_:b337063508 . _:b337063366 "19"^^ . _:b337063511 . . . _:b337063510 . _:b337064312 . _:b337063368 "18"^^ . _:b337063505 . _:b337063369 "17"^^ . _:b337064263 . _:b337063504 . _:b337063370 "17"^^ . _:b337063645 . _:b337063507 . . _:b337063371 "17"^^ . _:b337063907 . _:b337063506 . _:b337063372 "17"^^ . _:b337063373 "16"^^ . _:b337063517 . . _:b1842507 "After store depletion, Ca2+ release by the EF-hand is likely to cause a conformational change in STIM1, as it does in other EF-hand\u2013containing proteins (Herzberg et al., >>1986<<; Zhang et al., 1995)." . _:b337064308 . _:b337063374 "16"^^ . _:b337063516 . . _:b1842436 . _:b337063375 "16"^^ . _:b337063519 . _:b337063368 . _:b337064152 . . _:b337064189 . _:b337064528 . . _:b337063376 "16"^^ . _:b337063518 . . _:b337063513 . _:b337063377 "16"^^ . _:b337064050 . _:b337063378 "16"^^ . _:b337063512 . _:b337063379 "16"^^ . . _:b337063515 . _:b337063398 . . . _:b337063380 "16"^^ . _:b337063514 . _:b337063399 . . _:b337063787 . _:b337063381 "15"^^ . _:b337063525 . _:b337063382 "15"^^ . _:b1842513 . _:b337063524 . _:b337063383 "15"^^ . _:b337063527 . . _:b337063384 "14"^^ . _:b337064108 . _:b337063526 . _:b337063391 "13"^^ . _:b337063385 "14"^^ . _:b337063521 . _:b337064443 . _:b337063390 "13"^^ . _:b337063386 "14"^^ . _:b337063554 . _:b337063478 . _:b337063520 . _:b337063387 "14"^^ . _:b337063523 . _:b337063388 "14"^^ . _:b337063522 . _:b337063389 "14"^^ . _:b337063533 . _:b337063532 . _:b337063535 . _:b337064161 . _:b1842449 "Over the past decade, several classes of models have been proposed to describe how this communication might occur (Berridge, 2004; Parekh and Putney, >>2005<<). These include conformational coupling between proteins in the ER and plasma membranes, possibly between STIM1 and the CRAC channel itself. In an extension of this model, referred to as \u201Cinduced-coupling\u201D or \u201Csecretion-like coupling,\u201D" . _:b337063399 "12"^^ . _:b337063534 . . _:b337063398 "12"^^ . . _:b337063529 . _:b337063528 . _:b337063397 "13"^^ . _:b337063531 . _:b337063396 "13"^^ . . _:b337063530 . _:b337063395 "13"^^ . _:b337063357 . _:b337063541 . _:b337063394 "13"^^ . _:b337063593 . . _:b337063540 . _:b337063393 "13"^^ . _:b337064085 . _:b337064517 . _:b337063505 . _:b337063543 . _:b337063392 "13"^^ . _:b337063407 "11"^^ . _:b337063542 . _:b337063429 . _:b337063406 "11"^^ . . _:b337063537 . . . _:b337063405 "11"^^ . _:b337063536 . _:b1842479 . _:b337063404 "11"^^ . _:b337063539 . _:b337064487 . _:b337063403 "12"^^ . _:b337063538 . _:b337064197 . _:b337063402 "12"^^ . . _:b337063549 . _:b1842431 . _:b337064196 . _:b337063401 "12"^^ . _:b337063548 . _:b337064199 . _:b337063400 "12"^^ . _:b337063551 . _:b337063842 . _:b337064226 . _:b337064198 . _:b337063949 . _:b337063415 "11"^^ . . _:b337063550 . _:b337064193 . _:b337063414 "11"^^ . _:b337063545 . . _:b337064192 . . _:b337064070 . . _:b337063413 "11"^^ . _:b337063544 . _:b337064195 . _:b337063412 "11"^^ . _:b337063547 . _:b337064194 . _:b337063411 "11"^^ . _:b337063546 . . _:b337064205 . _:b337063410 "11"^^ . . . _:b337063557 . . _:b337064204 . _:b337063409 "11"^^ . _:b337064271 . _:b337063556 . _:b337064207 . _:b337063408 "11"^^ . _:b337063559 . _:b337063423 "10"^^ . _:b337064147 . _:b337064206 . _:b337063558 . _:b337063459 . _:b337064201 . _:b337063422 "10"^^ . _:b337063420 . _:b337063553 . _:b337063421 "10"^^ . _:b337064200 . _:b337063552 . _:b337063420 "10"^^ . _:b337064203 . . _:b337063555 . _:b1842471 "The formation of STIM1 puncta in areas of the ER close to the plasma membrane led us to consider the \u201Cinduced coupling\u201D model of store-operated Ca2+ entry previously proposed (Patterson et al., 1999; Venkatachalam et al., >>2002<<). This model states that the ER moves to the plasma membrane to establish protein\u2013protein interactions necessary for SOC activation." . _:b337063419 "10"^^ . _:b337064202 . _:b337063977 . _:b337063455 . _:b337063554 . . _:b337064213 . _:b337063411 . _:b337063418 "10"^^ . . . _:b337063565 . _:b337064212 . _:b337063417 "11"^^ . _:b337063564 . _:b337064215 . _:b337064163 . _:b337063416 "11"^^ . _:b337063427 . _:b337063567 . _:b337063836 . _:b337064214 . . _:b337063566 . . _:b337064209 . _:b337063561 . _:b337064208 . _:b337063994 . _:b337063560 . _:b1842482 "These measurements describe a critical step in the control of store-operated Ca2+ entry and at the ultrastructural level define a structure that mediates the activation of CRAC channels in the plasma membrane (Luik et al., >>2006<<)." . _:b337064211 . _:b337063563 . . _:b337064210 . _:b337063465 . . . _:b337063562 . _:b337064221 . _:b337063613 . _:b337063573 . _:b337064030 . _:b337064220 . _:b337063572 . _:b337064223 . . _:b337063575 . _:b337064222 . _:b337063574 . _:b337064442 . _:b337064217 . . _:b337063569 . _:b337064216 . _:b337064280 . _:b337063568 . _:b337064219 . _:b337063571 . _:b337064218 . _:b337063570 . . . _:b337064229 . _:b337063581 . _:b337064228 . _:b337063580 . _:b337064231 . _:b337064398 . _:b337063583 . _:b337064230 . _:b1842503 . . _:b337063582 . . _:b337064225 . _:b337063577 . _:b337064224 . _:b337064447 . . . _:b337063576 . _:b337064227 . _:b337063579 . _:b337064226 . _:b337063578 . _:b337064237 . _:b1842497 . . _:b337064404 . _:b337063825 . _:b337063589 . . _:b337064236 . _:b337063588 . _:b337064239 . _:b337063789 . _:b337063591 . _:b337064238 . _:b337063590 . _:b337064233 . _:b337063585 . _:b337064232 . . _:b337063584 . _:b337063769 . _:b337064235 . . _:b337063587 . _:b337063479 . _:b337064234 . _:b1842463 "As reported previously in intact cells (Liou et al., >>2005<<; Zhang et al., 2005), passive depletion of Ca2+ stores during whole-cell recording led to the appearance of GFP-STIM1 puncta near the plasma membrane (Fig." . . _:b337063586 . _:b337063767 . _:b337064091 . _:b337064245 . _:b337063597 . . _:b337064244 . _:b337064526 . _:b337063596 . _:b337064247 . . . _:b337063599 . _:b337064246 . . _:b337063598 . _:b1842489 "In addition, they failed to detect staining of the cell surface with antibodies that would be expected to react with YFP-STIM1 at the cell surface, although the data were not published. A second study, by Zhang et al. (>>2005<<), concluded that store depletion causes significant translocation of STIM1 from the ER into the plasma membrane, where it was proposed to stimulate Ca2+ entry by activating CRAC channels or by assembling with additional STIM1 monomers or" . _:b337064241 . _:b337063593 . _:b337063902 . _:b337064240 . . _:b337064548 . _:b337063592 . _:b337064243 . _:b337064024 . _:b337063595 . _:b337063434 . . . _:b337064242 . _:b337063594 . _:b337064253 . . _:b337063605 . _:b337064252 . _:b337064582 . _:b337063604 . _:b337064255 . _:b337063607 . . _:b337063816 . _:b337064254 . . _:b337063606 . _:b337064249 . _:b337063601 . _:b337064562 . _:b337064248 . _:b337063600 . _:b337064251 . _:b337064056 . _:b337063603 . . _:b337064250 . _:b337064170 . _:b337063710 . _:b337063602 . _:b337064261 . _:b337063613 . _:b337064260 . . _:b337063612 . _:b337064263 . _:b337063615 . . _:b337064262 . _:b337064408 . _:b337063614 . _:b337064257 . . . _:b337063609 . _:b337064256 . . _:b337063608 . . _:b337063689 . _:b337064259 . _:b337063393 . _:b337063611 . _:b337064258 . . _:b337063610 . _:b337063901 . _:b337064269 . _:b337063621 . _:b337064268 . . _:b337064324 . _:b337063620 . _:b337064271 . _:b337064344 . _:b337063623 . _:b337064270 . _:b337063622 . _:b337064138 . _:b337064265 . _:b337063617 . _:b337064264 . _:b337064633 . . _:b337063616 . _:b337064267 . _:b337063619 . _:b337063600 . _:b337064266 . _:b337063618 . . _:b337064093 . _:b337064277 . _:b337063629 . _:b337064276 . _:b337063628 . _:b337064279 . _:b337063631 . _:b337064278 . _:b337063806 . _:b337063630 . _:b337064083 . _:b337064273 . _:b337063625 . _:b337064187 . _:b337064272 . _:b337063624 . _:b337064275 . _:b337063627 . _:b337064274 . . . _:b337063626 . _:b337063941 "3"^^ . _:b337064285 . _:b337063940 "3"^^ . _:b337063637 . _:b337064284 . _:b337063943 "3"^^ . _:b337063636 . _:b337064287 . _:b337063942 "3"^^ . _:b337063639 . _:b337064288 . _:b337064286 . _:b337063937 "3"^^ . _:b337063638 . _:b337063679 . _:b337064281 . _:b337063936 "3"^^ . . _:b337063633 . _:b337063415 . _:b337063760 . _:b337064280 . _:b337063939 "3"^^ . _:b337063632 . _:b337064283 . _:b337063938 "3"^^ . _:b337063635 . _:b337064282 . _:b337063949 "3"^^ . _:b1842472 "the localization of HRP fusion proteins in the ER, Golgi, and transport vesicles has been achieved with very high contrast and without permeabilization, using peroxidase cytochemistry and conventional transmission EM (Connolly et al., >>1994<<; Dubois et al., 2001). Because the HRP reaction product is restricted to the lumen of the HRP-containing compartment, ER-localized STIM1 should be clearly distinguishable from STIM1 in the plasma membrane." . _:b337063634 . _:b337063611 . _:b337064293 . _:b337063948 "3"^^ . _:b337063645 . _:b337064292 . _:b337063951 "3"^^ . _:b337063644 . _:b337064295 . _:b337063950 "3"^^ . _:b337063647 . _:b337064294 . _:b337064277 . . _:b337063646 . _:b337063945 "3"^^ . _:b337064289 . _:b337063944 "3"^^ . _:b337063641 . _:b337063814 . _:b337063885 . _:b337064288 . _:b337063947 "3"^^ . _:b337063640 . _:b337063450 . _:b337064291 . _:b337064353 . . _:b337063643 . _:b337063946 "3"^^ . . . _:b337064290 . _:b337063906 . _:b337063957 "3"^^ . _:b337063642 . _:b337064301 . _:b337063956 "3"^^ . _:b337063653 . _:b337064287 . _:b337064300 . . _:b337064413 . _:b337063652 . _:b337063959 "3"^^ . _:b337064303 . _:b337063839 . _:b337063655 . _:b337063958 "3"^^ . _:b337064302 . _:b337063953 "3"^^ . _:b337063654 . _:b337064297 . _:b337064139 . . . _:b337063952 "3"^^ . _:b337063649 . _:b337063997 . _:b337063476 . . _:b337064296 . _:b337063955 "3"^^ . _:b337063648 . _:b337064299 . _:b337063954 "3"^^ . _:b337063651 . _:b337064298 . _:b337063965 "3"^^ . _:b337063650 . _:b337064309 . _:b337063964 "3"^^ . _:b337063661 . . _:b337064308 . _:b337063967 "3"^^ . _:b337063660 . . _:b337064311 . _:b337063966 "3"^^ . _:b337063663 . _:b337064521 . _:b337064310 . _:b337063961 "3"^^ . _:b337063662 . . _:b337064305 . _:b337063960 "3"^^ . _:b337063657 . _:b337064304 . . _:b337063963 "3"^^ . _:b337063656 . _:b337064307 . _:b337063962 "3"^^ . _:b337063659 . _:b337064306 . _:b337063973 "2"^^ . _:b337063658 . _:b337064317 . _:b337063972 "2"^^ . _:b337063669 . . _:b337064316 . _:b337063910 . _:b337063975 "2"^^ . _:b337063668 . _:b337064511 . _:b337064319 . _:b337063974 "2"^^ . _:b337063671 . . _:b337064318 . _:b337063969 "3"^^ . _:b337063670 . . _:b337064313 . _:b337064204 . . _:b337063665 . _:b337063968 "3"^^ . _:b337064312 . _:b337063971 "3"^^ . _:b337063664 . _:b337064315 . _:b337063970 "3"^^ . _:b337063667 . . . _:b337064314 . _:b337063981 "2"^^ . _:b337063666 . . _:b337064325 . _:b337063980 "2"^^ . _:b337063677 . _:b337064324 . _:b337063983 "2"^^ . _:b337063676 . _:b337064327 . _:b337063982 "2"^^ . _:b337064336 . _:b337063679 . _:b337064326 . _:b337063620 . _:b337063977 "2"^^ . _:b337063678 . . _:b337064321 . _:b337063976 "2"^^ . _:b337063673 . _:b337064320 . . _:b337063979 "2"^^ . _:b337064132 . _:b337063672 . _:b337064323 . _:b337063978 "2"^^ . _:b337063675 . _:b337064322 . _:b337063989 "2"^^ . _:b337063674 . _:b337064333 . _:b337063988 "2"^^ . _:b337063759 . _:b337064332 . _:b337063991 "2"^^ . _:b337063473 . _:b337064335 . _:b337063990 "2"^^ . _:b337064334 . . _:b337063985 "2"^^ . . _:b337064329 . _:b337063984 "2"^^ . . _:b337064328 . _:b337063987 "2"^^ . . _:b337064331 . _:b337064236 . . _:b1842474 . _:b337063986 "2"^^ . _:b337064330 . _:b337064510 . _:b337063997 "2"^^ . _:b337064341 . . _:b1842472 . _:b337063996 "2"^^ . _:b337064340 . _:b337063999 "2"^^ . _:b337064343 . _:b337063998 "2"^^ . _:b337063804 . _:b337064342 . . _:b337063993 "2"^^ . _:b337064337 . _:b337063992 "2"^^ . . _:b337063438 . _:b337064307 . _:b337064336 . _:b337063995 "2"^^ . _:b337064576 . _:b337064339 . _:b337063994 "2"^^ . _:b337064338 . _:b337064005 "2"^^ . _:b337063801 . _:b337064017 . _:b337064349 . _:b337064004 "2"^^ . . _:b337063587 . . _:b337064348 . _:b337064007 "2"^^ . . . _:b337064351 . . _:b337064006 "2"^^ . . _:b337064350 . . _:b337064001 "2"^^ . . _:b337064345 . _:b337064000 "2"^^ . _:b337064344 . _:b337064003 "2"^^ . . _:b337064347 . _:b337064492 . _:b337064002 "2"^^ . . _:b337064346 . _:b337064013 "2"^^ . _:b337064357 . . _:b337064012 "2"^^ . _:b337064559 . _:b337064356 . _:b337064015 "2"^^ . _:b337064615 . _:b337064372 . _:b337064359 . . _:b337064014 "2"^^ . _:b337064358 . _:b337064009 "2"^^ . _:b337063346 . _:b337064353 . _:b337064008 "2"^^ . _:b337064352 . _:b337064011 "2"^^ . _:b1842451 . _:b337064564 . _:b337064355 . _:b337064010 "2"^^ . _:b337064354 . _:b337064021 "2"^^ . _:b337064365 . _:b337064020 "2"^^ . _:b337064014 . _:b337063467 . _:b337064364 . _:b337064023 "2"^^ . _:b337064367 . _:b337064022 "2"^^ . _:b337064366 . _:b337064017 "2"^^ . _:b337064361 . _:b337064196 . _:b337064016 "2"^^ . _:b337064360 . _:b337064019 "2"^^ . _:b337064363 . _:b337064018 "2"^^ . _:b337064039 . _:b337064362 . _:b337064029 "2"^^ . _:b337064151 . . _:b337064373 . _:b337064028 "2"^^ . . _:b337064372 . _:b337064031 "2"^^ . _:b337064375 . _:b337063963 . _:b337064030 "2"^^ . _:b337064208 . _:b337064374 . . _:b337064025 "2"^^ . _:b337063810 . _:b337064369 . _:b337064024 "2"^^ . _:b337064368 . _:b337063456 . _:b337064027 "2"^^ . _:b337064371 . _:b337064026 "2"^^ . _:b337064041 . . _:b337064370 . _:b337064037 "2"^^ . _:b337064291 . _:b337063397 . _:b337064381 . _:b337064036 "2"^^ . _:b337064380 . _:b337064039 "2"^^ . . . _:b337064383 . _:b337064038 "2"^^ . _:b337064382 . _:b337064033 "2"^^ . _:b337064325 . _:b337064377 . . _:b337064032 "2"^^ . . . _:b337064376 . _:b337064035 "2"^^ . _:b337063869 . _:b337064379 . _:b337064034 "2"^^ . _:b337064378 . _:b337064045 "2"^^ . . . . _:b337064389 . _:b337064044 "2"^^ . . _:b337063655 . . . _:b337064388 . _:b337064047 "2"^^ . _:b337063642 . _:b337064391 . _:b337064046 "2"^^ . _:b337064390 . _:b337064041 "2"^^ . _:b337064385 . _:b337064040 "2"^^ . _:b337064384 . . _:b337064043 "2"^^ . _:b337064387 . _:b337064042 "2"^^ . _:b337064386 . . _:b337064053 "2"^^ . _:b337063708 . _:b337064166 . _:b337064397 . _:b337064252 . _:b337064052 "2"^^ . _:b337064396 . _:b1842497 "Junctional ER has been observed before in many cell types, including Jurkat cells, Xenopus laevis oocytes, smooth muscle, neurons, and yeast, though a role in store-operated Ca2+ entry has never been established (Henkart et al., >>1976<<; Gardiner and Grey, 1983; Takeshima et al., 2000; Pichler et al., 2001; Dadsetan et al., 2005)." . . _:b337064055 "2"^^ . . _:b337064399 . . _:b337064054 "2"^^ . _:b337064398 . _:b337064049 "2"^^ . _:b1842450 "In an extension of this model, referred to as \u201Cinduced-coupling\u201D or \u201Csecretion-like coupling,\u201D the depleted ER would move to the cell periphery to establish these physical coupling sites (Venkatachalam et al., >>2002<<). Store depletion may also promote vesicle fusion and insertion of CRAC channels or STIM1 into the plasma membrane. Finally, depletion could activate CRAC channels at a distance through the release of a diffusible messenger from the ER." . _:b337064393 . _:b337064048 "2"^^ . _:b337064448 . _:b337064392 . _:b337064051 "2"^^ . _:b337064508 . _:b337063564 . _:b337064395 . _:b337064050 "2"^^ . _:b337064394 . _:b337064061 "2"^^ . _:b337063580 . _:b337064405 . . _:b337064060 "2"^^ . _:b337064299 . _:b337063584 . _:b337064404 . _:b337064063 "2"^^ . . _:b337064407 . _:b337064062 "2"^^ . _:b337063544 . _:b337064406 . . _:b337064057 "2"^^ . . _:b337063741 . _:b337064401 . _:b337064056 "2"^^ . _:b337064400 . _:b337064059 "2"^^ . _:b337063809 . . _:b337064403 . . _:b337064058 "2"^^ . . _:b337064402 . _:b337064069 "2"^^ . _:b337063609 . _:b337064413 . _:b337064068 "2"^^ . . _:b337064412 . _:b337064071 "2"^^ . _:b337063768 . _:b337064063 . _:b337064415 . _:b337064070 "2"^^ . _:b337064414 . _:b337064065 "2"^^ . . _:b337064409 . _:b337064064 "2"^^ . _:b337064174 . . _:b337064408 . _:b337064067 "2"^^ . _:b337064411 . _:b337064066 "2"^^ . _:b337064410 . _:b337064077 "2"^^ . _:b337064421 . _:b337063916 . _:b337064076 "2"^^ . . _:b337064420 . _:b337064079 "2"^^ . _:b337064150 . _:b337064423 . _:b337064095 . _:b337064078 "2"^^ . _:b337064422 . _:b337064073 "2"^^ . . . _:b337064417 . _:b337064072 "2"^^ . . _:b337064416 . _:b337064075 "2"^^ . _:b1842495 . _:b337064419 . _:b337063365 . _:b337064074 "2"^^ . _:b337063890 . _:b337064418 . _:b337064085 "2"^^ . _:b337064429 . _:b337064084 "2"^^ . _:b337064533 . _:b337064323 . _:b337064428 . _:b337064087 "2"^^ . _:b337064431 . _:b337064086 "2"^^ . _:b337064430 . _:b337064081 "2"^^ . . _:b337064425 . _:b337064080 "2"^^ . . _:b337063776 . _:b337064444 . _:b337064424 . _:b337064083 "2"^^ . _:b337064427 . _:b337064082 "2"^^ . . _:b337064426 . _:b337064093 "2"^^ . _:b337064027 . _:b337064437 . . _:b337064092 "2"^^ . . _:b337063608 . . _:b337064436 . _:b337064095 "2"^^ . _:b337064439 . _:b337064094 "2"^^ . _:b337064438 . _:b337064089 "2"^^ . _:b337064433 . . _:b337064414 . _:b337064088 "2"^^ . _:b337064432 . _:b337063772 . _:b337064091 "2"^^ . _:b337064435 . _:b337063999 . _:b337064090 "2"^^ . _:b337064434 . _:b337064101 "2"^^ . . _:b337064652 . _:b337064445 . _:b337064100 "2"^^ . _:b337064444 . _:b337064103 "2"^^ . . . _:b337064447 . _:b337064102 "2"^^ . _:b337064446 . _:b337064097 "2"^^ . . _:b337064441 . _:b337064096 "2"^^ . _:b1842439 . _:b337064440 . _:b337064099 "2"^^ . _:b337064443 . _:b337064098 "2"^^ . _:b337064442 . _:b337064109 "2"^^ . _:b337063941 . _:b337064108 "2"^^ . . _:b337063940 . . _:b337064111 "2"^^ . _:b337063943 . . _:b337064110 "2"^^ . _:b337063590 . _:b337063942 . _:b337064105 "2"^^ . . _:b337063937 . _:b337064104 "2"^^ . . _:b337064109 . . _:b337063936 . . _:b337064107 "2"^^ . _:b337063939 . _:b337064106 "2"^^ . . _:b337063938 . _:b337064117 "2"^^ . _:b337064090 . _:b337063949 . _:b337064116 "2"^^ . _:b1842483 "Previous studies have shown that the mean time course of STIM1 puncta formation in cell populations is slow and roughly parallels the activation of SOCs measured in different cells (Liou et al., >>2005<<; Zhang et al., 2005)." . . _:b337063948 . _:b337064119 "2"^^ . _:b337063951 . _:b337064118 "2"^^ . . _:b337063950 . . _:b337064113 "2"^^ . . _:b337064294 . . _:b337063945 . _:b337064112 "2"^^ . _:b337064110 . _:b337063944 . . _:b337064115 "2"^^ . _:b337063486 . _:b337063947 . _:b337064114 "2"^^ . . _:b337063704 . _:b337063946 . _:b337064125 "2"^^ . _:b337063654 . _:b337063957 . _:b337064124 "2"^^ . . _:b337063435 . _:b337064172 . _:b337063956 . _:b337063589 . _:b337064127 "2"^^ . . _:b337063959 . _:b337064126 "2"^^ . _:b337063958 . _:b337064121 "2"^^ . _:b337063780 . _:b337063953 . _:b337064120 "2"^^ . _:b337063952 . _:b337064123 "2"^^ . . _:b337063955 . _:b337064122 "2"^^ . _:b337063845 . _:b337063954 . _:b337064221 . _:b337064133 "2"^^ . . _:b337063965 . _:b337064077 . _:b337064132 "2"^^ . . _:b337063964 . _:b337064135 "2"^^ . _:b337063967 . _:b337064134 "2"^^ . . _:b337063966 . _:b337063361 . _:b337064129 "2"^^ . _:b337063961 . _:b337064128 "2"^^ . _:b337063752 . _:b337063960 . _:b337064131 "2"^^ . _:b337063963 . _:b337064130 "2"^^ . . _:b337063962 . . _:b337064141 "2"^^ . _:b337063470 . _:b337063396 . _:b337063888 . _:b337063973 . _:b337064140 "2"^^ . _:b337063972 . _:b337064143 "2"^^ . _:b1842506 "A produce similar inhibitory effects in a variety of cells, including platelets, corneal epithelial cells, and pancreatic acinar cells (Rosado et al., 2005), they do not affect ICRAC in rat basophlic leukemia cells (Bakowski et al., >>2001<<). Our observation of depletion-dependent formation of ER\u2013plasma membrane contacts in Jurkat cells provides the first direct evidence in favor of the induced-coupling hypothesis." . _:b337063975 . _:b337064142 "2"^^ . . _:b337063974 . _:b337064137 "2"^^ . _:b337063969 . _:b337064136 "2"^^ . _:b1842491 . _:b337063968 . _:b337064139 "2"^^ . _:b337063971 . _:b337064138 "2"^^ . . . _:b337063970 . _:b337064149 "2"^^ . _:b337063981 . _:b337064148 "2"^^ . _:b337063333 . _:b337063975 . . _:b337063980 . _:b337064151 "2"^^ . _:b337063332 . _:b337063651 . _:b337063983 . _:b337064150 "2"^^ . _:b337063335 . _:b337063982 . _:b337064145 "2"^^ . _:b337063887 . _:b337063334 . _:b337064201 . _:b337063865 . _:b337063977 . _:b337063647 . _:b337064144 "2"^^ . . _:b337063329 . _:b337064249 . _:b337063976 . _:b337064147 "2"^^ . _:b337063328 . _:b337063979 . _:b337064146 "2"^^ . _:b337063331 . . . _:b337063978 . _:b337063783 . _:b337064157 "2"^^ . _:b337063330 . _:b337063989 . _:b337064156 "2"^^ . _:b337064122 . _:b337063341 . _:b337064146 . _:b337063988 . _:b337064159 "2"^^ . . _:b337063340 . _:b337064498 . _:b337063991 . _:b337064158 "2"^^ . _:b337063343 . _:b337063990 . _:b337064153 "2"^^ . _:b337064632 . . _:b337063342 . _:b337064010 . _:b337063985 . _:b337064152 "2"^^ . _:b337063337 . _:b337063984 . _:b337064155 "2"^^ . _:b337063336 . _:b337063987 . _:b337064154 "2"^^ . _:b337063339 . . _:b337063986 . _:b337064165 "2"^^ . _:b337063338 . _:b337063997 . _:b1842505 "Although jasplakinolide and calyculin A produce similar inhibitory effects in a variety of cells, including platelets, corneal epithelial cells, and pancreatic acinar cells (Rosado et al., >>2005<<), they do not affect ICRAC in rat basophlic leukemia cells (Bakowski et al., 2001)." . . _:b337064164 "2"^^ . . _:b337063349 . _:b337063996 . _:b337064167 "2"^^ . _:b337063433 . _:b337063348 . . _:b337063999 . _:b337064166 "2"^^ . _:b337063351 . _:b337063971 . _:b337063998 . _:b337064161 "2"^^ . _:b337063350 . _:b337063993 . _:b337064160 "2"^^ . _:b337063345 . _:b337063992 . _:b337064163 "2"^^ . _:b337063344 . _:b337063995 . _:b337064162 "2"^^ . _:b337064193 . _:b337063347 . . _:b337063994 . _:b337064173 "2"^^ . _:b337063346 . . _:b337063781 . _:b337064005 . _:b337064370 . _:b337064167 . _:b337064172 "2"^^ . _:b337064154 . _:b337063357 . _:b1842488 "Liou et al. (>>2005<<) reported that STIM1 accumulates in ER near the plasma membrane." . _:b337064004 . . _:b337064175 "2"^^ . _:b337063356 . _:b337064568 . _:b337064007 . _:b337064174 "2"^^ . _:b337063988 . _:b337063359 . _:b337064006 . _:b337064169 "2"^^ . _:b337063358 . . _:b337064001 . _:b337064168 "2"^^ . _:b337063353 . _:b337064000 . _:b337064171 "2"^^ . _:b337063352 . _:b337064168 . _:b337064003 . _:b337064170 "2"^^ . . _:b337063355 . _:b337064002 . _:b337064181 "2"^^ . _:b337063354 . _:b337064613 . . _:b337064013 . . _:b337064180 "2"^^ . _:b337063365 . _:b337064245 . _:b337064012 . _:b337064183 "2"^^ . _:b337063364 . _:b337064015 . _:b337064182 "2"^^ . _:b337063367 . . _:b337064014 . _:b337064177 "2"^^ . _:b337063366 . . _:b337064009 . _:b337064176 "2"^^ . _:b337063361 . . _:b337064008 . _:b337064179 "2"^^ . . _:b337063360 . _:b337064011 . _:b337064165 . _:b337064178 "2"^^ . _:b337063363 . _:b337064301 . _:b337064010 . _:b337064189 "2"^^ . _:b337063362 . . _:b337064021 . _:b337064188 "2"^^ . _:b337064092 . _:b337063373 . _:b337064020 . . _:b337064191 "2"^^ . _:b337063372 . _:b337064023 . _:b337064190 "2"^^ . _:b337063560 . _:b337063375 . _:b337064022 . . _:b337064185 "2"^^ . _:b337063374 . _:b337064388 . _:b337063981 . _:b337063711 . _:b1842508 . _:b337064017 . _:b337064067 . _:b337064184 "2"^^ . . _:b337063369 . . _:b337064016 . _:b337064187 "2"^^ . _:b337063390 . _:b337063368 . _:b337064019 . . _:b337064186 "2"^^ . _:b337063348 . _:b337063371 . _:b337064018 . _:b337064197 "2"^^ . . _:b337063370 . _:b337064029 . _:b337064196 "2"^^ . _:b337063381 . _:b337064028 . _:b337064199 "2"^^ . _:b337063380 . _:b337063516 . _:b337063367 . . _:b337064031 . _:b337064198 "2"^^ . _:b337063383 . _:b337064030 . _:b337064193 "2"^^ . _:b337063382 . _:b1842487 "The 6\u201310-s latency between STIM1 accumulation and ICRAC activation suggests that there may be additional channel activation steps subsequent to redistribution or that a critical level of STIM1 or Ora1 (Luik et al., >>2006<<) must be reached before activation can occur." . _:b337064025 . . _:b337064192 "2"^^ . _:b337063377 . . _:b337064024 . _:b337064195 "2"^^ . _:b337063376 . _:b337064027 . _:b337064494 . _:b337064194 "2"^^ . _:b337063379 . _:b337064026 . _:b337064205 "2"^^ . _:b337063378 . _:b337064037 . _:b337064204 "2"^^ . _:b337063389 . _:b337064036 . _:b337064207 "2"^^ . _:b337063388 . . _:b1842479 "In terms of width and proximity to the plasma membrane, these ER\u2013plasma membrane contact sites resemble the \u201Cjunctional ER\u201D described in many cell types (Gardiner and Grey, 1983; Takeshima et al., 2000; Baumann and Walz, >>2001<<; Levine, 2004)." . _:b337064039 . _:b337064206 "2"^^ . _:b337063391 . _:b337064456 . _:b337064038 . _:b337064201 "2"^^ . _:b337063390 . _:b337064033 . _:b337064200 "2"^^ . _:b337063385 . _:b337064032 . _:b337064472 . _:b337064203 "2"^^ . _:b337063384 . _:b337064035 . _:b337064202 "2"^^ . _:b337063387 . . _:b337064034 . . _:b337064213 "2"^^ . _:b337063386 . _:b337064577 . _:b337064045 . _:b337064212 "2"^^ . _:b337063397 . _:b337063918 . _:b337064044 . _:b337064215 "2"^^ . _:b337063396 . . _:b337064047 . _:b337064214 "2"^^ . _:b337063399 . _:b337064052 . _:b337064046 . _:b337064209 "2"^^ . _:b337063398 . _:b1842435 . _:b337064041 . _:b337063355 . _:b337064208 "2"^^ . _:b337063393 . _:b337063379 . _:b337064040 . _:b337064211 "2"^^ . _:b337064657 . _:b337063392 . _:b337063919 . _:b337064043 . _:b337063735 . _:b337064210 "2"^^ . _:b337063395 . _:b337064042 . _:b337063686 . _:b337064221 "2"^^ . _:b337063585 . _:b337063394 . _:b337063369 . _:b337064053 . _:b337064220 "2"^^ . _:b337063405 . . _:b337064052 . . _:b337064223 "2"^^ . _:b337063404 . _:b337063408 . _:b337064055 . _:b337064222 "2"^^ . _:b337064512 . _:b337063407 . _:b337064054 . _:b337063732 . _:b337064217 "2"^^ . _:b337063406 . _:b337064088 . _:b337064514 . _:b337064049 . _:b337064216 "2"^^ . _:b337063401 . _:b337064048 . _:b337064219 "2"^^ . _:b337063400 . _:b337064051 . _:b337063929 . _:b337063635 . _:b337064218 "2"^^ . . _:b337063403 . _:b337064050 . _:b337064100 . _:b337064229 "2"^^ . _:b337063402 . _:b337064061 . _:b337064228 "2"^^ . _:b337063413 . _:b337064060 . _:b337064231 "2"^^ . _:b337063412 . _:b337063833 . . _:b337064063 . _:b337064230 "2"^^ . _:b337063415 . . _:b337064062 . _:b337064225 "2"^^ . _:b337063414 . . _:b337064057 . _:b337064224 "2"^^ . _:b337063409 . _:b337064056 . _:b337064227 "2"^^ . _:b337064396 . _:b337063408 . _:b337064059 . . _:b337064226 "2"^^ . _:b337063411 . _:b337064058 . _:b337064237 "2"^^ . _:b337063410 . _:b337064057 . _:b337064069 . _:b337064236 "2"^^ . _:b337063421 . _:b337064173 . _:b337064068 . _:b337063690 . _:b337064239 "2"^^ . _:b337063420 . _:b337063974 . . _:b337064071 . _:b337064238 "2"^^ . _:b337063423 . _:b337064070 . _:b337064233 "2"^^ . _:b337063422 . _:b337063668 . _:b337064065 . _:b337064232 "2"^^ . _:b337063417 . _:b337064064 . . . _:b337064235 "2"^^ . _:b337063416 . _:b337064067 . _:b337064234 "2"^^ . _:b337063419 . _:b337064066 . . _:b337064245 "2"^^ . _:b337063418 . _:b337063923 . _:b337064077 . _:b337064244 "2"^^ . . . _:b337063884 . _:b337064076 . _:b337064247 "2"^^ . _:b337064079 . . _:b337064246 "2"^^ . _:b337064078 . _:b337064241 "2"^^ . _:b337064073 . _:b337064240 "2"^^ . . _:b1842486 "movement to the plasma membrane may limit the speed with which CRAC channels respond to changes in ER [Ca2+], which takes tens of seconds even in response to rapid IP3-induced Ca2+ release (Hoth and Penner, 1993; Prakriya and Lewis, >>2001<<). The 6\u201310-s latency between STIM1 accumulation and ICRAC activation suggests that there may be additional channel activation steps subsequent to redistribution or that a critical level of STIM1 or Ora1 (Luik et al., 2006) must be reached" . _:b337064072 . _:b337064243 "2"^^ . _:b337064634 . _:b337064075 . _:b337063490 . _:b337064242 "2"^^ . . _:b337064074 . _:b337064253 "2"^^ . _:b337064085 . _:b337063395 . _:b337064252 "2"^^ . _:b337064536 . _:b337064084 . _:b337064255 "2"^^ . _:b1842498 "observed before in many cell types, including Jurkat cells, Xenopus laevis oocytes, smooth muscle, neurons, and yeast, though a role in store-operated Ca2+ entry has never been established (Henkart et al., 1976; Gardiner and Grey, >>1983<<; Takeshima et al., 2000; Pichler et al., 2001; Dadsetan et al., 2005)." . _:b337064087 . . _:b337064254 "2"^^ . _:b337064086 . _:b337064249 "2"^^ . _:b1842461 "GFP-STIM1 behaved similarly to wild-type STIM1 and to the fluorescent protein\u2013labeled STIM1 constructs used by others (Liou et al., >>2005<<; Zhang et al., 2005) in that GFP-STIM1 was localized to the ER in resting cells (Fig." . . _:b337064081 . _:b337064065 . _:b337064248 "2"^^ . _:b337064080 . _:b337064251 "2"^^ . _:b337064083 . _:b337064250 "2"^^ . _:b337064082 . _:b337064261 "2"^^ . _:b337064093 . . _:b337064260 "2"^^ . _:b337064092 . _:b337064263 "2"^^ . _:b337064095 . _:b337064262 "2"^^ . _:b337064094 . _:b337064257 "2"^^ . . _:b337063883 . _:b337064089 . . _:b337064256 "2"^^ . _:b337064088 . _:b337064259 "2"^^ . _:b337064091 . . _:b337064258 "2"^^ . . _:b337064090 . _:b337064269 "2"^^ . _:b337064101 . _:b337064268 "2"^^ . _:b337064100 . _:b337064271 "2"^^ . _:b337064103 . _:b337064270 "2"^^ . _:b1842492 "However, the spatial resolution offered by indirect immunolabeling is at most 25\u201330 nm (Jorgensen and Jones, 1987; Kimura et al., >>1999<<), insufficient to rule out protein locations in ER located within 10\u201325 nm of the plasma membrane." . _:b337064102 . _:b337064265 "2"^^ . _:b337063371 . _:b337064097 . _:b337064264 "2"^^ . _:b337064096 . _:b337064258 . _:b337064267 "2"^^ . _:b337064099 . . _:b337064266 "2"^^ . _:b337063353 . _:b337064098 . _:b337063996 . _:b337064277 "2"^^ . . _:b337064109 . _:b337064276 "2"^^ . _:b337064646 . _:b337064108 . _:b337064279 "2"^^ . _:b337064111 . _:b337064278 "2"^^ . . _:b337064110 . _:b337064273 "2"^^ . _:b337063946 . _:b337064105 . . _:b337064272 "2"^^ . . _:b337064104 . . _:b337063695 . _:b337064275 "2"^^ . _:b337064107 . _:b337064274 "2"^^ . _:b337064106 . _:b337063913 . _:b337064285 "2"^^ . _:b337064117 . _:b337064284 "2"^^ . _:b337064116 . _:b337064282 . _:b337064287 "2"^^ . _:b337063545 . _:b337064119 . _:b337064286 "2"^^ . _:b1842478 "In terms of width and proximity to the plasma membrane, these ER\u2013plasma membrane contact sites resemble the \u201Cjunctional ER\u201D described in many cell types (Gardiner and Grey, 1983; Takeshima et al., >>2000<<; Baumann and Walz, 2001; Levine, 2004)." . _:b337064118 . _:b337064281 "2"^^ . . _:b337064113 . _:b337064280 "2"^^ . _:b337064462 . _:b337064112 . _:b337064283 "2"^^ . _:b337064115 . _:b337064282 "2"^^ . . _:b337064114 . _:b337064293 "2"^^ . _:b337064125 . _:b337064292 "2"^^ . _:b337063824 . _:b337064124 . _:b337063825 . _:b337063826 . _:b337064295 "2"^^ . _:b337063848 . _:b337063827 . . _:b337063828 . _:b337064127 . _:b337063829 . _:b337064228 . _:b337064214 . _:b337064294 "2"^^ . _:b337063830 . _:b337063831 . _:b337063832 . . _:b337064126 . _:b337063833 . . _:b337064289 "2"^^ . _:b337063834 . _:b337063835 . _:b337063836 . _:b337064121 . _:b337063837 . _:b337063838 . _:b337064288 "2"^^ . _:b337063839 . _:b337063808 . _:b337064120 . _:b337063809 . _:b337063810 . _:b337064291 "2"^^ . _:b337063811 . _:b337063812 . _:b337064123 . _:b337063813 . _:b337063814 . _:b337064290 "2"^^ . _:b337063815 . . _:b337063816 . _:b337064122 . _:b337063817 . _:b337063818 . _:b337064301 "2"^^ . . _:b337063819 . _:b337064114 . _:b337063820 . _:b337064133 . _:b337063821 . _:b337063822 . _:b337064300 "2"^^ . _:b337063823 . _:b337063856 . _:b337064132 . _:b337064476 . _:b337063857 . _:b337063858 . _:b337064303 "2"^^ . _:b337063859 . _:b337063860 . _:b337064135 . _:b337063861 . _:b337063862 . _:b337064529 . _:b337064302 "2"^^ . _:b337063863 . _:b337063864 . _:b337064134 . _:b337063865 . _:b337063866 . _:b337064297 "2"^^ . _:b337063867 . _:b337063868 . _:b337064129 . _:b337063869 . _:b337063870 . _:b337064296 "2"^^ . _:b337063871 . _:b337063618 . _:b337063840 . _:b337064128 . _:b337063841 . . _:b337063842 . _:b337064299 "2"^^ . _:b337063843 . _:b337063844 . _:b337064131 . _:b337063845 . . _:b337064298 "2"^^ . _:b337063846 . _:b337063847 . . _:b337063848 . _:b337064130 . _:b337063849 . _:b337063850 . _:b337064309 "2"^^ . _:b337063851 . _:b337063852 . . _:b337064141 . _:b337063853 . _:b337064069 . _:b337064308 "2"^^ . _:b337063854 . _:b337063855 . _:b337063888 . _:b337064140 . _:b337063889 . _:b337063890 . _:b337064311 "2"^^ . _:b337063891 . _:b337063892 . _:b337064143 . _:b337063893 . _:b337063894 . _:b337064310 "2"^^ . _:b337063895 . _:b337063896 . _:b337064142 . _:b337063897 . . _:b337063898 . _:b337064305 "2"^^ . _:b337063899 . . _:b337063900 . _:b337064137 . _:b337063901 . _:b337063902 . _:b337064304 "2"^^ . _:b337063903 . _:b337063872 . _:b337063687 . _:b337063873 . _:b337064136 . _:b337063874 . _:b337064307 "2"^^ . _:b337063875 . _:b337063876 . _:b337064139 . _:b337063877 . _:b337063878 . _:b337064306 "2"^^ . _:b337063879 . _:b337063880 . _:b337064138 . _:b337063881 . _:b337063347 . . _:b337063882 . _:b337064317 "2"^^ . _:b337063883 . _:b337063884 . _:b337064149 . _:b337063885 . _:b337063886 . _:b337064316 "2"^^ . _:b337063680 . _:b337063887 . _:b337064435 . _:b337063920 . _:b337064515 . _:b337064148 . _:b337063921 . _:b337063922 . _:b337064544 . _:b337064319 "2"^^ . _:b337063923 . . _:b337063924 . _:b337064151 . _:b337063925 . _:b337063926 . _:b337064318 "2"^^ . _:b337063927 . _:b337063928 . _:b337064150 . _:b337063929 . _:b337064195 . _:b337064313 "2"^^ . _:b337063930 . _:b337063931 . . _:b337063932 . _:b337064145 . _:b337063933 . _:b337063934 . _:b337064312 "2"^^ . _:b337063935 . _:b337063797 . _:b337063904 . _:b337064144 . _:b337063905 . _:b337063906 . _:b337064315 "2"^^ . _:b337063907 . _:b337063908 . _:b337064147 . _:b337063909 . _:b337063910 . _:b337064314 "2"^^ . _:b337063444 . _:b337063911 . _:b337063665 . _:b337063912 . . _:b337064146 . _:b337063913 . _:b337063914 . _:b337064325 "2"^^ . _:b337063915 . _:b337063916 . _:b337064157 . _:b337063917 . _:b337063918 . _:b337064324 "2"^^ . . _:b337063919 . _:b337063696 . _:b337064156 . _:b337064427 . _:b337063697 . _:b337063698 . _:b337064327 "2"^^ . _:b337063699 . . _:b337063700 . _:b337064159 . _:b337063701 . _:b337063702 . _:b337064326 "2"^^ . _:b337063672 . _:b337063703 . _:b337063704 . _:b337064158 . _:b337063705 . _:b337063706 . _:b337064321 "2"^^ . _:b337063707 . . _:b337063708 . _:b337064153 . _:b337064593 . _:b337063709 . _:b337063710 . _:b337064320 "2"^^ . _:b337063711 . _:b337063680 . _:b337064152 . _:b337063681 . _:b337063682 . _:b337064323 "2"^^ . _:b337063683 . _:b337063684 . _:b337064155 . _:b337063685 . _:b337063686 . _:b337064322 "2"^^ . _:b337063687 . _:b337063688 . _:b337064154 . _:b337063689 . _:b337063690 . _:b337064333 "2"^^ . _:b337063691 . _:b337063692 . _:b337064165 . _:b1842507 . _:b337063693 . _:b337063694 . _:b337064332 "2"^^ . _:b337063695 . _:b337063728 . _:b337064164 . _:b337063729 . _:b337063730 . _:b337064335 "2"^^ . _:b337063731 . _:b337063732 . _:b337064586 . _:b337064167 . _:b337063733 . _:b337063734 . _:b337064334 "2"^^ . . _:b337063735 . _:b337063736 . . _:b337064166 . _:b337063737 . _:b337063738 . _:b337064329 "2"^^ . _:b337063739 . . _:b1842503 "entry, in which depletion is thought to trigger movement of peripheral ER tubules to the plasma membrane, to allow ER proteins to activate plasma membrane SOCs through physical coupling (Patterson et al., 1999; Venkatachalam et al., >>2002<<). This hypothesis was originally proposed to explain the ability of jasplakinolide and the phosphatase inhibitor calyculin A to block store-operated Ca2+ entry in smooth muscle cells (Patterson et al., 1999)." . _:b337063740 . _:b337064161 . _:b337063741 . _:b337063483 . _:b337063742 . _:b337064328 "2"^^ . _:b337063743 . . _:b337063712 . _:b337064160 . _:b337063713 . _:b337063714 . _:b337064331 "2"^^ . . _:b337063715 . _:b337063549 . _:b337063716 . _:b337064163 . . _:b337063717 . _:b337063718 . _:b337064330 "2"^^ . . _:b337063719 . _:b337063720 . _:b337064162 . _:b337063721 . _:b337063722 . _:b337064341 "2"^^ . _:b337063723 . _:b337063724 . _:b337064173 . _:b337063725 . _:b337063726 . _:b337064340 "2"^^ . _:b337063727 . _:b1842508 "After store depletion, Ca2+ release by the EF-hand is likely to cause a conformational change in STIM1, as it does in other EF-hand\u2013containing proteins (Herzberg et al., 1986; Zhang et al., >>1995<<). This conformational change could lead to \u201Ctrapping\u201D and accumulation of Ca2+-free STIM1 in junctional ER by increasing STIM1's affinity for a protein in the plasma membrane. Similarly, Ca2+-free STIM1 could promote formation of new" . _:b337063760 . _:b337064172 . _:b337063761 . _:b337063762 . _:b337064343 "2"^^ . _:b337063763 . _:b337063926 . _:b337063764 . _:b337064175 . _:b337063765 . _:b337064376 . _:b337063766 . _:b337064342 "2"^^ . . _:b337063767 . _:b337063768 . _:b337064174 . _:b337063769 . _:b337063770 . _:b337064337 "2"^^ . _:b337063771 . _:b337063772 . _:b337064567 . _:b337064169 . _:b337063773 . _:b337063774 . _:b337064336 "2"^^ . . _:b337064595 . _:b337063775 . _:b337063744 . _:b337063328 . _:b337064168 . . _:b337063745 . _:b337064367 . _:b337063746 . _:b337064339 "2"^^ . _:b337063747 . _:b337063748 . _:b337064171 . _:b337064532 . . _:b337063749 . _:b337063750 . _:b337064338 "2"^^ . _:b337063751 . _:b337063752 . _:b337064170 . _:b337063753 . _:b337063754 . _:b337064349 "2"^^ . _:b337063824 . _:b337063755 . _:b337063756 . _:b337064181 . _:b337063757 . _:b337063758 . _:b337064348 "2"^^ . _:b337063759 . . _:b337063792 . _:b337064180 . _:b337063793 . _:b337063401 . _:b337064351 "2"^^ . _:b337063794 . _:b337063795 . _:b337063796 . _:b337064183 . _:b337063797 . _:b337063746 . _:b337063798 . _:b337064350 "2"^^ . . . _:b337063799 . _:b337063666 . _:b337063800 . _:b337064182 . _:b337063801 . _:b337063802 . _:b337064345 "2"^^ . _:b337063803 . _:b337063804 . _:b337064177 . _:b337063805 . _:b337063806 . _:b337064344 "2"^^ . _:b337063807 . _:b337063776 . _:b337064176 . _:b337063777 . _:b337064099 . _:b337064347 "2"^^ . _:b337063778 . _:b337063779 . _:b337063780 . _:b337064213 . _:b337064179 . _:b337063781 . . _:b337063782 . _:b337064346 "2"^^ . _:b337063783 . . _:b337063784 . _:b337064178 . _:b337063785 . _:b337063786 . _:b337064418 . _:b337064357 "2"^^ . _:b337063787 . _:b337063788 . _:b337064189 . _:b337063789 . _:b337063454 . . _:b337064234 . _:b337064356 "2"^^ . _:b337063790 . _:b337063791 . _:b337063568 . _:b337064188 . _:b337063569 . _:b337063570 . _:b337064359 "2"^^ . _:b337063571 . _:b337063572 . _:b337064191 . _:b337063573 . _:b337063574 . _:b337064358 "2"^^ . . _:b337063575 . _:b337063576 . _:b337064190 . _:b337064005 . _:b337063577 . _:b337063578 . _:b337064353 "2"^^ . _:b337063579 . _:b337063580 . _:b337064185 . _:b337063581 . _:b337063960 . _:b337063582 . _:b337064352 "2"^^ . _:b337063583 . _:b337063791 . _:b337063552 . _:b337064184 . _:b337063553 . _:b337063554 . _:b337064355 "2"^^ . _:b337063555 . _:b337063556 . _:b337064187 . _:b337063557 . _:b337063558 . _:b337064354 "2"^^ . . _:b1842504 . _:b337063559 . . _:b337063560 . _:b337064186 . _:b337063561 . _:b337063562 . _:b337064365 "2"^^ . _:b337063563 . _:b337063564 . . _:b337063565 . _:b337063566 . _:b337064364 "2"^^ . _:b337063567 . _:b337063600 . _:b337063601 . _:b337063602 . _:b337064367 "2"^^ . . _:b337063603 . _:b337063604 . _:b337063605 . _:b337063606 . _:b337064366 "2"^^ . _:b337063607 . _:b337063608 . _:b337063891 . _:b337063609 . _:b337063610 . _:b337064361 "2"^^ . _:b337063611 . _:b337063612 . _:b337063613 . _:b337063614 . _:b337064360 "2"^^ . _:b337063615 . . _:b337063584 . _:b337063585 . . _:b337064363 "2"^^ . _:b337063586 . _:b337063587 . _:b337063588 . _:b337063589 . _:b337063590 . _:b337064362 "2"^^ . _:b337063591 . _:b337063592 . _:b337063593 . . _:b337064373 "2"^^ . _:b337063594 . _:b337063595 . _:b337064206 . _:b337063596 . _:b337063597 . _:b337063598 . _:b337064372 "2"^^ . . _:b337063599 . _:b1842502 . _:b337063640 . _:b337063632 . _:b337063633 . _:b337063634 . _:b337064375 "2"^^ . _:b337063635 . _:b337064374 . _:b337063636 . _:b337063637 . _:b1842493 "In addition, the biotinylation was performed after 30 min of treatment with sarco(endo)plasmic reticulum Ca2+ ATPase inhibitors, and prolonged depletion of stores is known to impair retention of ER resident proteins (Booth and Koch, >>1989<<; Suzuki et al., 1991; Egan et al., 2002)." . _:b337063638 . _:b337064374 "2"^^ . _:b337063639 . _:b337064520 . _:b337063640 . _:b337063641 . _:b337063642 . _:b337064369 "2"^^ . _:b337063643 . _:b337063644 . _:b337063645 . _:b337063646 . _:b337064368 "2"^^ . _:b337063647 . _:b337063616 . _:b337063400 . _:b337063617 . _:b337063618 . _:b337064371 "2"^^ . _:b337063619 . _:b337064549 . _:b337063620 . _:b337063621 . _:b337063622 . _:b337064468 . _:b337064370 "2"^^ . _:b337064368 . _:b337063623 . _:b337064134 . _:b337063624 . _:b337063625 . . _:b337063626 . _:b337064381 "2"^^ . _:b337063627 . _:b337063628 . . _:b337063629 . _:b337063630 . _:b337064380 "2"^^ . _:b337063631 . _:b337063664 . _:b337064542 . _:b337063665 . _:b337063666 . _:b337064383 "2"^^ . _:b337063667 . _:b337064648 . _:b337063668 . _:b337063669 . _:b337063670 . _:b337064382 "2"^^ . _:b337063671 . _:b337063672 . . _:b337063673 . _:b337063674 . _:b337064377 "2"^^ . . _:b337063675 . _:b337063676 . . _:b337063677 . . _:b337063678 . _:b337064376 "2"^^ . _:b337063867 . _:b337063679 . _:b337063517 . _:b337063648 . _:b337063649 . _:b337063650 . _:b337064379 "2"^^ . _:b337063651 . _:b337063652 . _:b337063653 . _:b337063654 . _:b337064378 "2"^^ . _:b337063655 . _:b337063656 . _:b337063657 . _:b337063658 . _:b337064389 "2"^^ . _:b337063493 . _:b337063659 . _:b337063660 . . _:b337063661 . _:b337063662 . _:b337064388 "2"^^ . _:b337063663 . _:b337063440 . _:b337063441 . _:b337063442 . _:b337064391 "2"^^ . _:b337063443 . _:b337063444 . _:b337063445 . _:b337063446 . _:b337064390 "2"^^ . _:b337063447 . . _:b337063448 . _:b337063534 . _:b337063449 . _:b337063450 . _:b337064385 "2"^^ . _:b337064203 . _:b337063451 . _:b337063452 . _:b337063453 . . _:b337063454 . _:b337064384 "2"^^ . _:b337063455 . _:b337063424 . _:b337063425 . _:b337063426 . _:b337064387 "2"^^ . _:b337063427 . _:b337063811 . _:b337063428 . _:b337063429 . _:b337063430 . _:b337064386 "2"^^ . _:b337063431 . _:b337063432 . _:b337063433 . . . _:b337064397 "2"^^ . _:b337063434 . _:b337063435 . . _:b337063436 . _:b337063437 . _:b337063438 . _:b337064396 "2"^^ . _:b337063439 . _:b337063472 . . _:b337063473 . _:b337063474 . _:b337064399 "2"^^ . _:b337063475 . _:b337063476 . _:b337063477 . _:b337063439 . _:b337064398 "2"^^ . _:b337063478 . _:b337063479 . _:b337064495 . _:b337063480 . _:b337063481 . _:b337064355 . _:b337064393 "2"^^ . _:b337063482 . _:b337063483 . _:b337063484 . . _:b337063485 . _:b337063486 . _:b337064392 "2"^^ . _:b337063487 . _:b337063456 . _:b337063457 . _:b337063458 . _:b337064395 "2"^^ . _:b337063459 . _:b337063460 . _:b337063461 . _:b337063462 . _:b337064394 "2"^^ . _:b337063463 . _:b337063464 . _:b337064612 . . _:b337063658 . _:b337063465 . _:b337063466 . _:b337064405 "2"^^ . . _:b337063467 . _:b337064357 . _:b337063468 . _:b337063469 . . _:b337064404 "2"^^ . _:b337063470 . _:b337063471 . _:b1842470 . _:b337063504 . _:b337063505 . _:b337063506 . _:b337064407 "2"^^ . _:b337063507 . _:b337063508 . _:b337063509 . _:b337063510 . _:b337064406 "2"^^ . _:b337063511 . _:b337063512 . _:b337063513 . _:b337063514 . _:b337064401 "2"^^ . _:b337063515 . _:b337063516 . _:b337063517 . . _:b337064400 "2"^^ . _:b337063518 . _:b337063519 . _:b337063488 . _:b337063489 . _:b337063490 . _:b337064403 "2"^^ . _:b337063491 . _:b337063915 . _:b337063492 . . _:b337064045 . _:b337063691 . _:b337063493 . . _:b337064402 "2"^^ . _:b337063494 . . _:b337063495 . . . _:b337063496 . _:b337063497 . _:b337063498 . _:b337064413 "2"^^ . _:b337063499 . _:b1842500 "Jurkat cells, Xenopus laevis oocytes, smooth muscle, neurons, and yeast, though a role in store-operated Ca2+ entry has never been established (Henkart et al., 1976; Gardiner and Grey, 1983; Takeshima et al., 2000; Pichler et al., >>2001<<; Dadsetan et al., 2005)." . _:b337063500 . _:b337063501 . _:b337063813 . _:b337064412 "2"^^ . _:b337063502 . _:b337063503 . _:b337063694 . . _:b337063536 . _:b337063537 . _:b337063538 . _:b337064415 "2"^^ . _:b337063539 . _:b337063540 . _:b337064295 . _:b337063541 . _:b337063542 . _:b337064414 "2"^^ . _:b337063543 . _:b337063544 . _:b337063545 . _:b337063546 . _:b337064409 "2"^^ . _:b337063547 . _:b337063548 . _:b337063549 . _:b337063550 . _:b337064408 "2"^^ . _:b337063551 . _:b337063520 . _:b337063521 . _:b337063522 . _:b337064411 "2"^^ . _:b337063523 . _:b337063524 . _:b337063754 . _:b337063525 . _:b337063526 . _:b337064410 "2"^^ . _:b337063527 . _:b337063528 . _:b337063529 . _:b337064026 . _:b337063530 . _:b337064594 . _:b337064421 "2"^^ . _:b337063531 . _:b337063532 . _:b337063533 . _:b337064232 . _:b337064420 "2"^^ . _:b337063534 . _:b337063535 . _:b337064423 "2"^^ . _:b337064422 "2"^^ . _:b337064417 "2"^^ . _:b337064416 "2"^^ . . . _:b337064419 "2"^^ . _:b337064418 "2"^^ . _:b337063722 . _:b337064429 "2"^^ . . _:b337064428 "2"^^ . . _:b337063344 . _:b337063345 . _:b337063346 . _:b337064431 "2"^^ . _:b337063347 . _:b337063348 . _:b337063349 . _:b337063350 . _:b337064430 "2"^^ . _:b337063351 . _:b337063352 . _:b337063353 . _:b337063354 . _:b337064425 "2"^^ . _:b337063355 . . _:b337063356 . . _:b337063357 . _:b337063358 . _:b337064424 "2"^^ . _:b337063359 . _:b337063552 . _:b337063328 . _:b337063329 . _:b337063330 . _:b337064452 . _:b337064427 "2"^^ . _:b337063331 . _:b337063332 . _:b337064635 . _:b337064044 . _:b337063333 . _:b337063334 . _:b337064426 "2"^^ . _:b337063335 . _:b337063336 . _:b337063337 . _:b337063338 . _:b337064437 "2"^^ . _:b337064411 . _:b337063339 . _:b337063340 . _:b337063341 . _:b337063957 . _:b337063342 . _:b337064436 "2"^^ . _:b337063343 . _:b337063376 . _:b337063377 . _:b337063378 . _:b337064439 "2"^^ . _:b337063379 . _:b337063380 . _:b337063381 . _:b337063382 . _:b337064438 "2"^^ . _:b337063383 . _:b337063878 . _:b337063384 . _:b337063385 . _:b337063386 . _:b337064433 "2"^^ . . _:b337063387 . _:b337063388 . _:b337063389 . _:b337063390 . _:b337064432 "2"^^ . . . _:b337063391 . _:b337063360 . _:b337063361 . _:b337063362 . _:b337064435 "2"^^ . _:b337063363 . _:b337063364 . _:b337063365 . _:b337063366 . _:b337064434 "2"^^ . _:b337063367 . _:b337063368 . _:b337063369 . . _:b337064445 "2"^^ . _:b337063370 . . . _:b337063371 . . _:b337063372 . _:b337063373 . _:b337064342 . _:b337064444 "2"^^ . _:b337063374 . . _:b337063375 . _:b337063408 . _:b337063409 . _:b337063410 . _:b337064447 "2"^^ . _:b337063411 . _:b337063412 . . _:b337063413 . _:b337063846 . _:b337064446 "2"^^ . _:b337063414 . _:b337063415 . _:b337063416 . _:b337063417 . _:b337063418 . _:b337064441 "2"^^ . _:b337063419 . _:b337063420 . _:b337063561 . _:b337063421 . . _:b337064440 "2"^^ . _:b337063422 . _:b337063423 . _:b337063392 . _:b337063393 . _:b337063394 . _:b337064443 "2"^^ . _:b337063395 . _:b337064622 . _:b337063396 . . _:b337063397 . _:b337063398 . _:b337064442 "2"^^ . _:b337063399 . _:b337063400 . _:b337063401 . _:b337063402 . _:b337063403 . _:b337063404 . _:b337063405 . _:b337063406 . _:b337064617 . . _:b337063940 . _:b337063407 . . . . _:b337064300 . . _:b337063350 . . _:b337064310 . _:b1842475 "3; Liou et al., >>2005<<; Zhang et al., 2005) and confirm that the N terminus of STIM1 faces the ER lumen." . _:b1842433 "CRAC channels play a critical role in promoting gene expression during T cell activation, as shown by spontaneous mutations that abrogate Ca2+ influx and cause severe combined immunodeficiency in human patients (Partiseti et al., >>1994<<; Feske et al., 2005, 2006)." . . _:b337064454 . . . _:b337063860 . _:b337064240 . . _:b337064169 . . _:b337063543 . _:b337064434 . _:b337064003 . _:b337064133 . _:b337063976 . _:b337063540 . _:b337063356 . . _:b337064086 . . . _:b337064409 . _:b337064597 . . _:b337063423 . _:b337064309 . . _:b337064311 . . . _:b337063830 . _:b337064319 . _:b337063818 . _:b337063894 . _:b337064554 . . . . _:b337063807 . _:b337064599 . _:b337064475 . . _:b337064159 . _:b1842477 "In terms of width and proximity to the plasma membrane, these ER\u2013plasma membrane contact sites resemble the \u201Cjunctional ER\u201D described in many cell types (Gardiner and Grey, >>1983<<; Takeshima et al., 2000; Baumann and Walz, 2001; Levine, 2004)." . _:b337063777 . . _:b337063634 . . . _:b1842446 "Liou et al. (>>2005<<) concluded that puncta formed in the ER near the plasma membrane." . . . . _:b337063341 . . . _:b337064349 . _:b337063896 . . _:b1842499 "cell types, including Jurkat cells, Xenopus laevis oocytes, smooth muscle, neurons, and yeast, though a role in store-operated Ca2+ entry has never been established (Henkart et al., 1976; Gardiner and Grey, 1983; Takeshima et al., >>2000<<; Pichler et al., 2001; Dadsetan et al., 2005)." . _:b337064248 . . _:b337063638 . . _:b1842484 "Previous studies have shown that the mean time course of STIM1 puncta formation in cell populations is slow and roughly parallels the activation of SOCs measured in different cells (Liou et al., 2005; Zhang et al., >>2005<<). However, the precise timing of STIM1 accumulation and ICRAC could easily be obscured by the cell-to-cell variation within populations; for this reason, it is important to measure the two simultaneously in the same cell. In this study," . . _:b337064439 . . . . _:b337064362 . . _:b337063351 . . . . . _:b337063556 . _:b337064430 . _:b337064239 . . . _:b337064538 . . _:b337064537 . _:b337064364 . _:b337064160 . . . _:b337063614 . . _:b337064123 . _:b337063717 . . . . . . _:b337064021 . _:b337064155 . . . _:b337063491 . . . _:b337064210 . _:b337063362 . . . _:b337063701 . . . _:b337063582 . . _:b1842493 . _:b337063453 . _:b337064381 . _:b337063729 . . _:b337063363 . _:b337063578 . . . _:b337064585 . . _:b337064392 . . _:b337064470 . . _:b337063571 . _:b1842453 "materials and methods" . _:b337064255 . . _:b337063764 . _:b337063385 . . . _:b337064209 . _:b337063709 . _:b1842454 "Jurkat E6-1 cells (American Type Culture Collection) were grown as previously described (Prakriya and Lewis, >>2001<<). Cells were transiently transfected with a gene pulser (Bio-Rad Laboratories) 48\u201372 h before experiments." . _:b337063404 . . . _:b337064354 . . . _:b337063331 . . . _:b337064314 . . . . _:b337063747 . _:b337063872 . _:b337064250 . . . _:b337063987 . _:b337063959 . . . . _:b337063372 . _:b337064038 . _:b337064653 . . . . _:b337064641 . . _:b337063643 . . _:b337063595 . _:b337063391 . _:b1842470 "The formation of STIM1 puncta in areas of the ER close to the plasma membrane led us to consider the \u201Cinduced coupling\u201D model of store-operated Ca2+ entry previously proposed (Patterson et al., >>1999<<; Venkatachalam et al., 2002). This model states that the ER moves to the plasma membrane to establish protein\u2013protein interactions necessary for SOC activation." . _:b337064101 . . . . . _:b337064073 . . . . _:b1842500 . _:b337064592 . _:b337064593 . . _:b337064594 . _:b337063897 . _:b337064595 . _:b337063382 . _:b337064596 . . _:b337064597 . . . _:b337064598 . _:b337064599 . _:b337063445 . _:b337064600 . _:b337064601 . _:b337064602 . _:b337064603 . _:b337063414 . _:b337064604 . . _:b337064605 . _:b337064606 . _:b337064081 . _:b337064607 . _:b337064576 . _:b337064577 . _:b337063871 . _:b337064578 . _:b337064579 . . _:b337064580 . _:b337063472 . _:b337064581 . _:b337064582 . _:b337064583 . _:b337064584 . _:b337064585 . _:b337063922 . _:b337064586 . _:b337064587 . _:b337064588 . _:b337064589 . _:b337064590 . _:b337064591 . _:b337064624 . _:b337064625 . _:b337064626 . . _:b337064627 . _:b337064628 . _:b337064629 . _:b337064630 . _:b337064631 . _:b337064632 . . _:b337064633 . _:b337064634 . _:b337064464 . _:b337064635 . _:b337064636 . _:b337064637 . _:b337064638 . _:b337064639 . _:b337064608 . . _:b337064609 . _:b337064610 . _:b337064611 . _:b337064612 . _:b337064613 . _:b337064614 . _:b337064615 . _:b337064616 . _:b337064617 . _:b337064618 . _:b337064619 . _:b337064647 . _:b337064620 . _:b337064621 . _:b337064622 . _:b337064623 . _:b337063876 . _:b337064656 . _:b337064657 . _:b337064658 . . _:b337064535 . _:b337063852 . _:b1842447 "On the other hand, Zhang et al. (>>2005<<) concluded that store depletion causes STIM1 to enter the plasma membrane, based on immuno-EM and surface biotinylation studies." . _:b337064640 . _:b337064641 . _:b337064642 . _:b337064643 . _:b337064257 . _:b337064644 . _:b337064645 . _:b337064322 . _:b337064646 . _:b337064647 . _:b337064648 . _:b337063597 . _:b337064649 . _:b337064650 . _:b337064651 . _:b337064652 . _:b337064653 . _:b337064654 . _:b337064655 . _:b337064610 . _:b337063730 . _:b337063855 . . _:b337063998 . . _:b337063386 . _:b337064199 . . _:b337064102 . . _:b337064464 . _:b337064465 . _:b337064466 . _:b337064467 . _:b337064468 . _:b337064469 . _:b337064470 . _:b337064471 . . _:b337064472 . _:b337064473 . _:b337064474 . . _:b337064475 . . _:b337064476 . _:b337064477 . _:b337064478 . . _:b337064479 . _:b337064448 . _:b337064449 . _:b337064450 . _:b337064451 . _:b337063373 . _:b337064452 . _:b337064453 . _:b337064454 . _:b337064455 . _:b337064456 . _:b337064457 . _:b337063499 . _:b337064458 . _:b337064459 . _:b337064460 . _:b337064461 . _:b337064462 . . _:b337064463 . _:b337064496 . _:b337064497 . . _:b337064498 . _:b337064499 . _:b337064500 . _:b337064501 . . _:b337064502 . _:b337064503 . _:b337064504 . . _:b337064505 . . _:b337064506 . _:b337064507 . _:b337064508 . _:b337064509 . _:b337064510 . _:b337064511 . _:b337064480 . _:b337064481 . _:b337064482 . _:b337064483 . _:b337064484 . _:b337064485 . _:b337064486 . _:b337064487 . _:b337064488 . _:b337064489 . _:b337064490 . _:b337064491 . _:b337064492 . _:b337064493 . _:b337064494 . _:b337064495 . . _:b337064528 . _:b337064529 . _:b337063452 . _:b337064530 . _:b337064531 . _:b337064532 . . _:b337064533 . _:b337064534 . _:b337064535 . _:b337063800 . _:b337064536 . _:b337064537 . _:b337064538 . _:b337064539 . _:b337064540 . . _:b337064541 . _:b337064542 . _:b337064543 . _:b337064512 . _:b337064459 . _:b337064513 . _:b337064514 . _:b337064515 . _:b337064516 . _:b337064517 . . _:b337064518 . _:b337064519 . _:b337064520 . _:b337064521 . _:b337064522 . . _:b337064523 . _:b337064524 . _:b337064525 . _:b337064320 . _:b337064526 . . _:b337064527 . _:b337063511 . _:b337064560 . _:b337064561 . _:b337064562 . _:b337064563 . . _:b337064564 . _:b337064565 . _:b337064566 . _:b337064567 . _:b337064568 . _:b337064569 . _:b337063657 . _:b337064570 . _:b337064571 . . _:b337064572 . _:b337064573 . _:b337064574 . _:b337064575 . _:b337064544 . _:b337064545 . _:b337064546 . _:b337064286 . _:b337064547 . _:b337064548 . _:b337064549 . _:b337064550 . _:b337064551 . _:b337064552 . _:b337064553 . _:b337064554 . _:b337064555 . _:b337064330 . _:b337064556 . _:b337064557 . _:b337064558 . _:b337064162 . _:b337064559 . _:b337064019 . _:b337064336 . _:b337064337 . _:b337064338 . _:b337064339 . _:b337064340 . _:b337064341 . _:b337064342 . _:b337064343 . _:b337064344 . _:b337064345 . _:b337064346 . _:b337064347 . _:b337064348 . _:b337064349 . . _:b337064350 . _:b337064351 . _:b337064320 . _:b337064321 . _:b337064322 . _:b337064323 . _:b337064324 . _:b337064325 . _:b337064326 . _:b337064327 . _:b337063778 . _:b337064328 . _:b337064329 . _:b337064330 . _:b337064331 . _:b337064332 . _:b337064333 . _:b337064334 . _:b337064335 . _:b337064368 . _:b337064369 . _:b337064370 . . _:b337064371 . _:b337064372 . _:b337064373 . _:b337064374 . _:b337064550 . _:b337063954 . _:b337064375 . _:b337064376 . _:b337064377 . _:b337064592 . _:b337064378 . _:b337064379 . _:b337064410 . _:b337064380 . _:b337064381 . _:b337064382 . _:b337064460 . . _:b337064383 . _:b337064352 . _:b337064353 . _:b337064354 . _:b337064355 . _:b337064356 . _:b337064357 . _:b337064358 . _:b337064359 . _:b337064360 . . _:b1842495 "after 30 min of treatment with sarco(endo)plasmic reticulum Ca2+ ATPase inhibitors, and prolonged depletion of stores is known to impair retention of ER resident proteins (Booth and Koch, 1989; Suzuki et al., 1991; Egan et al., >>2002<<). There is evidence for STIM1 expression in the plasma membrane based on immunolabeling and biotinylation of K562 cells, although the same caveats about biotinylation apply to this study (Manji et al., 2000)." . _:b337064361 . _:b337064362 . . _:b337064363 . . _:b337064364 . _:b337064365 . _:b337064366 . _:b337064367 . _:b337064400 . . _:b1842469 "3, A\u2013C), consistent with previous work (Liou et al., 2005; Zhang et al., >>2005<<). After store depletion, GFP-STIM1 accumulated in puncta close to the plasma membrane (Fig." . _:b337064401 . _:b337063965 . _:b337064402 . _:b337064403 . _:b337064404 . _:b337064405 . _:b337064406 . _:b337064407 . _:b337064408 . _:b337064409 . "PMC0" . _:b337064410 . _:b337064411 . _:b337064412 . _:b337064413 . _:b337063570 . . _:b337064414 . _:b337064415 . _:b337064384 . _:b337064087 . _:b337064385 . _:b337064386 . _:b337064387 . _:b337063857 . _:b337064388 . _:b337064389 . _:b337064293 . _:b337064390 . _:b337063861 . _:b337064391 . _:b337064392 . _:b337064393 . _:b337064394 . _:b337064395 . _:b337064396 . _:b337064397 . _:b337064398 . _:b337064399 . _:b337064432 . _:b337064433 . _:b337064275 . . _:b337064434 . _:b337064435 . _:b337064436 . _:b337063405 . _:b337064437 . _:b337064438 . _:b337064439 . . _:b337064440 . _:b337064441 . _:b337064442 . _:b337064443 . . _:b337064444 . _:b337064445 . . _:b337064446 . _:b337063821 . . _:b337064447 . _:b337064416 . _:b337064417 . _:b337064071 . _:b337063588 . _:b337064418 . _:b337064419 . _:b337064420 . _:b337064421 . _:b337064422 . _:b337064423 . _:b337064424 . _:b337064425 . _:b337064426 . _:b337064427 . _:b337063934 . _:b337064428 . _:b337064429 . _:b337063440 . _:b337064430 . _:b337064431 . _:b337064208 . _:b337064209 . _:b337064210 . _:b337064211 . _:b337064212 . _:b337064213 . _:b337064214 . _:b337064215 . _:b337064216 . _:b337064217 . _:b337064218 . _:b337064219 . _:b337063329 . _:b337064220 . _:b337064221 . _:b337064222 . . _:b337064223 . _:b337064192 . _:b337064193 . _:b337064194 . _:b337064195 . . _:b337064196 . _:b337063522 . _:b337064197 . _:b337064198 . _:b337064199 . _:b337063659 . _:b337064200 . . _:b337064201 . _:b337064573 . _:b337064202 . _:b337064203 . _:b337064204 . _:b337064205 . _:b337064206 . _:b337064207 . _:b337064240 . _:b337064241 . _:b337064242 . _:b337064243 . _:b337064244 . _:b337063430 . _:b337064380 . _:b337064245 . _:b337064246 . _:b337063805 . _:b337064247 . _:b337064306 . . _:b337064248 . _:b337063956 . _:b337064249 . _:b337064250 . _:b337064251 . . _:b337064252 . _:b337064253 . _:b337064254 . _:b337063925 . _:b337064255 . _:b337064224 . _:b337064225 . _:b337064226 . _:b337064227 . _:b337064228 . _:b337064229 . _:b337064230 . _:b337064387 . _:b337063667 . _:b337064231 . . _:b337064232 . _:b337064371 . . _:b337064233 . _:b337064234 . _:b337064235 . . _:b337064236 . _:b337064237 . _:b337064238 . . _:b337064239 . _:b337064272 . _:b337064273 . _:b337064274 . _:b337064275 . _:b337064276 . _:b337064277 . _:b337064278 . _:b337064279 . _:b337064280 . _:b337064281 . _:b337064282 . . _:b337064283 . _:b337064284 . _:b337064285 . _:b337064286 . _:b337064287 . . _:b337063334 . . _:b337064256 . _:b337064257 . _:b337064258 . _:b337064259 . . _:b337064260 . _:b337064261 . _:b337064262 . _:b337064263 . _:b337064264 . _:b337064265 . _:b337064266 . _:b337064267 . _:b337064268 . _:b337064269 . _:b337064270 . _:b337064271 . _:b337064304 . _:b337064305 . _:b337064306 . _:b337064307 . _:b337064308 . _:b337064309 . _:b337064310 . _:b337064311 . . _:b337064312 . _:b337064313 . _:b337064314 . _:b337064315 . _:b337064316 . _:b337064317 . _:b337064318 . _:b337064507 . _:b337064319 . _:b337064288 . _:b337064289 . . _:b337064290 . _:b337064291 . _:b337064292 . _:b337064293 . _:b337064294 . _:b337064295 . _:b337064433 . _:b337064296 . _:b337064297 . _:b337064298 . _:b337064299 . . . _:b337064300 . _:b337064301 . _:b337064302 . _:b337064303 . _:b337064080 . _:b337064081 . _:b337064082 . _:b337064083 . _:b337064390 . _:b337064084 . _:b337064085 . _:b337064086 . _:b337064087 . _:b1842501 "laevis oocytes, smooth muscle, neurons, and yeast, though a role in store-operated Ca2+ entry has never been established (Henkart et al., 1976; Gardiner and Grey, 1983; Takeshima et al., 2000; Pichler et al., 2001; Dadsetan et al., >>2005<<). We found that store depletion causes STIM1 to accumulate in preexisting junctions (comprising approximately two thirds of the total junctions in depleted cells) as well as in newly formed junctions (comprising approximately one third;" . _:b337064088 . _:b337064089 . _:b337064090 . _:b337064091 . _:b337064620 . _:b337064092 . _:b337064093 . _:b337064094 . _:b337064095 . _:b337064064 . _:b337064065 . _:b337064066 . _:b337064067 . _:b337064068 . _:b337064069 . _:b337064070 . . _:b337064071 . _:b337064072 . _:b337064073 . _:b337064074 . _:b337064075 . _:b337064076 . _:b337063992 . _:b337064077 . _:b337064078 . _:b337064079 . . _:b337064112 . _:b337064113 . _:b337064114 . _:b337064115 . _:b337064116 . _:b337064117 . _:b337064140 . _:b337063756 . _:b337064118 . . _:b337064119 . _:b337064120 . _:b337063496 . _:b337064121 . _:b337064122 . _:b337064123 . _:b337064124 . _:b337064125 . _:b337064126 . _:b337064127 . . _:b337064096 . _:b337064097 . _:b337063474 . _:b337064098 . _:b337064099 . _:b337064100 . _:b337064101 . _:b337064102 . _:b337064103 . _:b337064104 . _:b337064105 . _:b337064278 . _:b337064106 . _:b337064107 . _:b337064591 . _:b337064108 . _:b337064109 . _:b337064110 . _:b337064111 . . _:b337064144 . _:b337063575 . _:b337064145 . _:b337064146 . _:b337064147 . _:b337064148 . _:b337064149 . _:b337064150 . _:b337064151 . _:b337064152 . _:b337064458 . _:b337064153 . _:b337063392 . _:b337064154 . _:b337064155 . _:b337064156 . _:b337064157 . _:b337064158 . _:b337064600 . _:b337064159 . _:b337064128 . _:b337064129 . _:b337064130 . _:b337064131 . _:b337064132 . _:b337064133 . . _:b337064134 . _:b337064135 . _:b337064136 . _:b337064137 . _:b337064138 . . _:b337064139 . . _:b337064140 . _:b337064141 . _:b337064142 . . _:b337064143 . _:b337064176 . _:b337064177 . _:b337064178 . _:b337064179 . _:b337064180 . _:b337064181 . _:b337063817 . _:b337064182 . _:b337063903 . _:b337064183 . _:b337064184 . _:b337064185 . _:b337064186 . _:b337064187 . _:b337064188 . _:b337064189 . _:b337063862 . _:b337064190 . _:b337064191 . . _:b337064160 . . _:b337064161 . _:b337064162 . . _:b337064163 . _:b337064265 . . _:b337064164 . _:b337064165 . . _:b337064166 . _:b337063931 . _:b337064167 . _:b337064168 . _:b337064169 . _:b337064170 . _:b337063376 . _:b337064171 . . _:b337064172 . _:b337064173 . _:b337064174 . _:b1842467 "GFP fluorescence is pH sensitive, decreasing by >80% from pH 7.0 to 5.0 (Elsliger et al., >>1999<<). If store depletion triggers GFP-STIM1 insertion into the plasma membrane, then the GFP will be exposed extracellularly and therefore be susceptible to quenching at low pH. We used TIRF imaging to compare the acid-induced quenching of" . _:b337064175 . _:b337063612 . _:b337063952 . . _:b337063953 . _:b337063954 . . _:b337063955 . _:b337063956 . . _:b337063957 . _:b337063958 . _:b337063959 . _:b337063960 . _:b337063961 . . _:b337063962 . _:b337063963 . _:b337063964 . _:b337063965 . _:b337064107 . _:b337063966 . _:b337063967 . _:b337063936 . _:b337063937 . . _:b337063938 . _:b337063671 . _:b337063939 . _:b337063940 . _:b337063941 . _:b337063942 . . _:b337063943 . _:b337063944 . _:b337063945 . _:b337063946 . _:b337063947 . _:b337064598 . _:b337063948 . . _:b337063949 . _:b337063950 . _:b337063951 . _:b337063984 . _:b337063985 . _:b337063986 . _:b337063987 . _:b337063988 . _:b337063989 . _:b337063990 . . _:b337063991 . _:b337063992 . . _:b337063930 . _:b337063993 . _:b337063994 . _:b337063995 . . _:b337063996 . _:b337063997 . _:b337063820 . . _:b337063998 . _:b337063999 . _:b337063968 . _:b337063969 . _:b337063970 . _:b337063971 . _:b337064075 . _:b337063972 . _:b337063973 . . . _:b337063840 . _:b337063974 . . _:b337063975 . _:b337063976 . _:b337063977 . _:b337063785 . _:b337063978 . _:b337063979 . _:b337063771 . _:b337063980 . _:b337063981 . _:b337063982 . _:b337063983 . _:b337064016 . _:b337064017 . _:b337064018 . _:b337064019 . _:b337064020 . _:b337064021 . _:b337064022 . _:b337064023 . _:b337064024 . _:b337064025 . _:b337064026 . _:b337064027 . . _:b337064028 . . _:b337064029 . _:b337064030 . . _:b337064031 . _:b337064000 . _:b337064001 . _:b337063412 . _:b337064002 . . _:b337064003 . _:b337064004 . . _:b337064005 . _:b337064006 . _:b337064007 . _:b337064008 . _:b337064009 . _:b337064010 . _:b337064011 . _:b337064012 . _:b337064013 . . . . _:b337064014 . _:b337063475 . _:b337064015 . . _:b337064048 . _:b337064049 . _:b337064050 . . _:b337064051 . . _:b337064052 . _:b337064053 . _:b337064054 . . _:b337064055 . _:b337064056 . _:b337063932 . _:b337064057 . . _:b337064058 . _:b337064059 . _:b337064060 . _:b337063698 . _:b337064061 . _:b337064385 . _:b337064062 . _:b337064063 . . _:b337063703 . _:b337064032 . _:b337064033 . _:b337064034 . _:b337064035 . _:b337064036 . _:b337064037 . _:b337064038 . _:b337064039 . . _:b337064040 . _:b337064041 . _:b337064042 . . _:b337064043 . _:b337064044 . _:b337064045 . _:b337063488 . _:b337064046 . _:b337064047 . . _:b337064556 . . _:b337064171 . _:b337064455 . . . _:b337064463 . . _:b337063487 . _:b337064486 . _:b1842504 "This hypothesis was originally proposed to explain the ability of jasplakinolide and the phosphatase inhibitor calyculin A to block store-operated Ca2+ entry in smooth muscle cells (Patterson et al., >>1999<<). Both compounds promote polymerization of cortical actin, which was proposed to create a physical barrier preventing the movement of ER to docking sites at the plasma membrane. Although jasplakinolide and calyculin A produce similar" . _:b337063422 . _:b337063943 . _:b337064060 . . . . . _:b1842441 "domain predicted to face the ER lumen, and mutations of residues that are expected to reduce STIM1's affinity for Ca2+ constitutively activate store-operated Ca2+ entry in cells with full Ca2+ stores (Liou et al., 2005; Zhang et al., >>2005<<). Interestingly, store depletion causes wild-type STIM1 to redistribute from a diffuse ER localization into puncta located at the cell periphery." . _:b337064297 . _:b337063503 . _:b337063636 . . _:b1842439 "In a major advance, two groups recently used RNAi-based screens to identify stromal interacting molecule 1 (STIM1) as an essential, conserved regulator of store-operated Ca2+ entry (Liou et al., 2005; Roos et al., >>2005<<). Current evidence suggests that STIM1 is the Ca2+ sensor for store depletion. STIM1 has an EF-hand domain predicted to face the ER lumen, and mutations of residues that are expected to reduce STIM1's affinity for Ca2+ constitutively" . . _:b337063364 . _:b337063917 . _:b337064446 . . . . . . _:b337063964 . . . . . . . . _:b1842466 "A recent study reported that store depletion causes STIM1 to translocate from the ER into the plasma membrane, where it might directly interact with or form CRAC channels (Zhang et al., >>2005<<). To test whether STIM1 is inserted into the plasma membrane, we performed fluorescence-quenching experiments with GFP-STIM1. GFP fluorescence is pH sensitive, decreasing by >80% from pH 7.0 to 5.0 (Elsliger et al., 1999). If store" . _:b337064233 . . . _:b337063573 . _:b337063675 . _:b337064000 . . . . . . _:b337064157 . _:b337063532 . _:b337063558 . _:b337064394 . _:b337064391 . _:b337064106 . . _:b337064654 . . _:b337064575 . . . _:b1842457 . _:b1842480 . _:b337064397 . . . _:b337064113 . _:b337063850 . _:b337064499 . _:b337064260 . _:b337064519 . . . . _:b337063480 . . . _:b337063995 . _:b337064164 . _:b337064246 . _:b337063539 . . . _:b337063463 . . _:b337063702 . _:b337064539 . _:b337064570 . . _:b337064395 . _:b337064547 . _:b337063449 . _:b337063485 . _:b337063502 . _:b337064565 . _:b337063520 . _:b337063648 . . _:b337064431 . _:b337063874 . _:b337063548 . _:b337064500 . . _:b337063799 . _:b337064078 . _:b337063858 . _:b1842456 . _:b337063970 . _:b337064256 . . . _:b337064130 . _:b337063868 . . . . . _:b337064175 . _:b1842437 . _:b337063375 . . . _:b1842512 "complexes through coiled-coil interactions; a classic example involves the SNARE proteins, which mediate vesicle docking and fusion through formation of a four-stranded coiled-coil complex measuring \u223C12 nm in length (Sutton et al., >>1998<<). Thus, the 10\u201325-nm separation we have measured between ER tubules and the plasma membrane may be small enough to permit interactions between proteins in the two opposing membranes as well as rapid diffusion of a soluble messenger." . . . . _:b337064329 . . . . . . _:b337064318 . . . _:b337064406 . . _:b337063419 . . . _:b337063563 . _:b1842449 . . . . . _:b337063388 . . _:b337064503 . . . _:b337063447 . . _:b337063723 . . _:b337064587 . . . _:b337063692 . . . . _:b337063670 . . . _:b337064574 . . _:b337063866 . . _:b337063808 . _:b1842462 "GFP-STIM1 behaved similarly to wild-type STIM1 and to the fluorescent protein\u2013labeled STIM1 constructs used by others (Liou et al., 2005; Zhang et al., >>2005<<) in that GFP-STIM1 was localized to the ER in resting cells (Fig." . _:b337063530 . . . . _:b1842492 . . . _:b337064356 . _:b337063881 . . _:b337063339 . . . _:b337063432 . . . . _:b337064244 . . . . _:b337064143 . . _:b337063359 . _:b337064043 . . . _:b337063469 . . _:b337063551 . _:b1842474 "In a previous study, an ER-targeted HRP in transfected fibroblast and epithelial cells appeared in the nuclear envelope and in serpentine cytoplasmic tubules, consistent with localization in the ER (Connolly et al., >>1994<<). In transfected Jurkat cells with full Ca2+ stores, both HRP-ER (Fig. 5, A and B) and HRP-STIM1 (Fig." . . _:b1842460 "cell populations has been shown to occur on average with roughly the same time course as CRAC channel activation, a direct comparison of STIM1 puncta formation and ICRAC activation has not been done (Liou et al., 2005; Zhang et al., >>2005<<). If the formation of STIM1 puncta is necessary for CRAC channel activation, it must precede channel opening." . _:b337063726 . . . _:b1842491 "However, the spatial resolution offered by indirect immunolabeling is at most 25\u201330 nm (Jorgensen and Jones, >>1987<<; Kimura et al., 1999), insufficient to rule out protein locations in ER located within 10\u201325 nm of the plasma membrane." . . . . _:b337064658 . . _:b337064352 . _:b337063508 . _:b337064432 . . . _:b337063822 . _:b337063504 . . _:b337064315 . . . . _:b337064105 . _:b337064369 . . . _:b337064298 . . _:b1842502 "model for store-operated Ca2+ entry, in which depletion is thought to trigger movement of peripheral ER tubules to the plasma membrane, to allow ER proteins to activate plasma membrane SOCs through physical coupling (Patterson et al., >>1999<<; Venkatachalam et al., 2002). This hypothesis was originally proposed to explain the ability of jasplakinolide and the phosphatase inhibitor calyculin A to block store-operated Ca2+ entry in smooth muscle cells (Patterson et al., 1999)." . . . . _:b337064098 . . _:b337064267 . . _:b337063853 . _:b337063739 . . . _:b337064273 . . _:b337063538 . _:b337064358 . . . _:b337064036 . _:b337063762 . _:b337063937 . _:b1842509 "Overexpression of junctate induces and/or stabilizes ER\u2013plasma membrane contact sites in HEK293 cells, and knock down of junctate by RNAi reduces the amount of junctional ER (Treves et al., >>2004<<). Further studies will be needed to test whether junctate plays a role and to identify other proteins that may be involved in forming new sites of junctional ER and in trapping STIM1 in puncta." . . _:b337064384 . _:b337064327 . _:b337063677 . . _:b337063550 . . _:b337064502 . _:b1842436 . . _:b337064645 . _:b1842437 . _:b337064437 . . _:b1842438 . _:b337064051 . _:b1842439 . _:b1842432 . _:b337064064 . _:b1842433 . _:b337064126 . _:b337064480 . _:b1842434 . _:b337063856 . _:b1842435 . . _:b1842444 . _:b1842445 . _:b1842446 . _:b337064624 . _:b1842447 . . _:b1842440 . . . _:b1842441 . _:b337063827 . . _:b1842442 . . _:b1842443 . . . _:b1842452 . _:b337063425 . _:b337063546 . _:b1842453 . _:b1842454 . . _:b1842455 . _:b1842448 . . . _:b1842449 . . _:b1842448 . _:b1842450 . _:b337063343 . _:b1842462 . _:b1842451 . _:b1842460 . _:b1842460 . _:b1842461 . _:b1842462 . _:b337064117 . . _:b1842463 . _:b1842456 . _:b1842457 . _:b1842458 . _:b337064262 . _:b1842459 . _:b1842468 . _:b1842469 . _:b337064429 . _:b1842470 . . _:b1842471 . . . _:b1842464 . _:b1842465 . _:b1842466 . _:b1842467 . _:b1842447 . _:b337064340 . . _:b1842476 . _:b337064008 . _:b1842477 . . _:b1842445 . . _:b1842478 . _:b337063757 . _:b337063596 . _:b337064313 . _:b1842479 . . _:b1842443 . _:b1842472 . . _:b337063629 . _:b1842473 . _:b1842441 . . _:b1842474 . . _:b1842475 . _:b337064216 . _:b1842484 . _:b1842484 . . _:b1842485 . _:b337063523 . _:b1842486 . . _:b337063417 . _:b1842487 . . _:b337063619 . _:b1842480 . _:b1842481 . . _:b1842482 . _:b1842483 . _:b337064290 . _:b1842492 . . _:b1842493 . _:b337064501 . _:b337063352 . . _:b1842494 . _:b1842490 . _:b1842495 . _:b1842488 . _:b337063942 . . _:b1842489 . _:b1842489 . _:b1842490 . _:b337063446 . _:b1842491 . . _:b337064422 . _:b1842500 . _:b337063684 . _:b1842501 . _:b1842481 _:b1842482 . _:b1842469 . _:b1842481 _:b1842483 . _:b1842481 _:b1842484 . _:b337063653 . _:b1842481 _:b1842485 . _:b1842502 . _:b1842481 _:b1842486 . _:b1842466 . _:b1842481 _:b1842487 . _:b1842481 _:b1842488 . _:b337063664 . _:b1842481 _:b1842489 . _:b1842503 . _:b1842481 _:b1842490 . . _:b1842481 _:b1842491 . _:b1842481 _:b1842492 . _:b1842481 _:b1842493 . _:b1842496 . _:b1842481 _:b1842494 . _:b1842464 . _:b1842481 _:b1842495 . _:b337064589 . _:b337063864 . _:b1842497 . _:b1842512 . . _:b1842498 . . _:b1842499 . . . _:b1842508 . _:b1842476 . _:b1842509 . _:b1842510 . _:b1842511 . _:b337064001 . . _:b1842504 . . _:b1842505 . _:b337063832 . _:b1842506 . _:b1842507 . . _:b337063854 . . . _:b337063515 . . _:b1842512 . _:b1842481 _:b1842496 . _:b1842481 _:b1842497 . _:b1842513 . _:b1842481 _:b1842498 . _:b1842481 _:b1842499 . _:b1842481 _:b1842500 . _:b1842481 _:b1842501 . _:b1842481 _:b1842502 . _:b1842481 _:b1842503 . _:b1842481 _:b1842504 . _:b1842481 _:b1842505 . _:b1842490 "Several possibilities may reconcile our conclusions with the results of Zhang et al. (>>2005<<), who based their argument for insertion on three lines of evidence. The first was immunofluorescence, in which the overlap of STIM1 with ER and cytosolic markers appeared to decrease after store depletion." . _:b1842445 "The kinetics of STIM1 redistribution has been reported in HeLa cells and Jurkat cells using total internal reflection fluorescence (TIRF) and confocal microscopy (Liou et al., 2005; Zhang et al., >>2005<<). Although puncta formation is generally slow, like CRAC current (ICRAC) activation, quantitative comparisons have not been made between redistribution and ICRAC activation in single cells, which is essential for testing causality." . _:b1842481 _:b1842506 . _:b1842481 _:b1842507 . _:b337064623 . _:b1842481 _:b1842508 . _:b1842481 _:b1842509 . _:b1842481 _:b1842510 . _:b1842481 _:b1842511 . _:b1842481 _:b1842512 . _:b1842481 _:b1842513 . . . _:b337064186 . . _:b337063577 . _:b337063815 . _:b337064473 . _:b337064125 . . _:b337064274 . _:b337063579 . . _:b1842458 _:b1842460 . _:b1842458 _:b1842461 . _:b1842458 _:b1842462 . _:b1842458 _:b1842463 . _:b337063676 . _:b337064603 . _:b1842458 _:b1842459 . _:b337064438 . . . . _:b1842458 _:b1842476 . _:b1842458 _:b1842477 . _:b1842458 _:b1842478 . _:b1842458 _:b1842479 . _:b1842458 _:b1842472 . _:b1842458 _:b1842473 . _:b1842458 _:b1842474 . _:b1842453 _:b1842454 . _:b1842458 _:b1842475 . _:b337063879 . _:b337064326 . _:b1842453 _:b1842455 . _:b1842453 _:b1842456 . _:b1842458 _:b1842468 . _:b1842458 _:b1842469 . _:b1842453 _:b1842457 . _:b1842458 _:b1842470 . _:b1842458 _:b1842471 . _:b337063826 . _:b1842458 _:b1842464 . _:b1842458 _:b1842465 . _:b1842458 _:b1842466 . _:b1842458 _:b1842467 . . . . _:b337064241 . _:b1842458 _:b1842480 . . _:b337064490 . _:b337064614 . _:b337063497 . _:b337064571 . _:b337064415 . _:b337064061 . _:b337063566 . _:b337064525 . . . . . . _:b337063533 . _:b337064028 . _:b337064176 . . . _:b337063782 . . _:b1842444 "The kinetics of STIM1 redistribution has been reported in HeLa cells and Jurkat cells using total internal reflection fluorescence (TIRF) and confocal microscopy (Liou et al., >>2005<<; Zhang et al., 2005)." . _:b337064285 . . _:b337064523 . _:b337064142 . _:b1842431 _:b1842448 . _:b1842431 _:b1842449 . . _:b1842431 _:b1842450 . _:b1842431 _:b1842451 . _:b1842431 _:b1842452 . _:b337063766 . _:b1842431 _:b1842440 . _:b1842431 _:b1842441 . _:b1842431 _:b1842442 . _:b1842431 _:b1842443 . _:b1842431 _:b1842444 . _:b1842431 _:b1842445 . _:b1842431 _:b1842446 . _:b1842431 _:b1842447 . _:b1842431 _:b1842432 . _:b1842431 _:b1842433 . _:b1842431 _:b1842434 . _:b1842431 _:b1842435 . _:b1842431 _:b1842436 . _:b1842431 _:b1842437 . _:b1842431 _:b1842438 . . _:b1842431 _:b1842439 . . . . _:b337063834 . . . . . _:b337063527 . _:b337064478 . _:b337064144 . _:b337064296 . _:b1842452 "HRP-labeled proteins have been used to study subcellular localization with greater spatial resolution and better preservation of membrane structure than is possible with immuno-EM (Connolly et al., 1994; Dubois et al., >>2001<<)." . . . . . . _:b337063744 . _:b337064482 . _:b337063751 . . . . . _:b337064451 . _:b1842456 "Patch-clamp experiments were conducted in the standard whole-cell recording and perforated-patch configurations as previously described (Zweifach and Lewis, 1995; Bautista et al., >>2002<<). The internal solution for whole-cell recording contained 140 mM Cs aspartate, 3 mM MgCl2, 1 mM EGTA, and 10 mM Hepes, pH 7.2 with CsOH." . . _:b337064518 . _:b337064149 . _:b337064084 . _:b337064457 . _:b337063384 . . _:b337063843 . . . _:b337064037 . _:b337063442 . . . . _:b337064118 . _:b337064321 . _:b337064416 . . . _:b337064283 . . _:b337063661 . . _:b337063581 . _:b337064072 . . _:b337064235 . . _:b337064207 . . . _:b337063602 . _:b337063461 . _:b337064656 . _:b337063437 . _:b337063381 . . . _:b1842457 "After postfixation with 1% OsO4 and en bloc stain with 1% uranyl acetate, cells were further processed as previously described (Ahmari et al., >>2000<<) before embedding in Embed 812 (Electron Microscopy Sciences)." . . _:b337063498 . _:b337064302 . _:b337063607 . _:b337064373 . _:b337063366 . _:b337063492 . _:b337064566 . . _:b337063713 . _:b337063583 . _:b337063740 . . . . _:b337063354 . . _:b337063536 . _:b337064054 . . _:b337064202 . _:b337063494 . _:b337063727 . _:b1842494 "was performed after 30 min of treatment with sarco(endo)plasmic reticulum Ca2+ ATPase inhibitors, and prolonged depletion of stores is known to impair retention of ER resident proteins (Booth and Koch, 1989; Suzuki et al., >>1991<<; Egan et al., 2002). There is evidence for STIM1 expression in the plasma membrane based on immunolabeling and biotinylation of K562 cells, although the same caveats about biotinylation apply to this study (Manji et al., 2000)." . . _:b1842432 . _:b337064483 . _:b1842510 "It is noteworthy that the cytoplasmic domain of STIM1 contains several putative protein interaction domains, including two \u03B1-helical coiled-coil domains and a proline-rich domain (Manji et al., >>2000<<; Williams et al., 2001)." . _:b337063424 . . . . . . _:b337064031 . _:b337063592 . . . _:b337064552 . . _:b337063599 . _:b337064509 . _:b337063793 . _:b337064141 . _:b337064655 . . _:b337064569 . . _:b1842448 "Over the past decade, several classes of models have been proposed to describe how this communication might occur (Berridge, >>2004<<; Parekh and Putney, 2005)." . _:b337063621 . _:b337064386 . _:b337064047 . _:b337064629 . . _:b337063682 . _:b337064453 . . _:b337064281 . . _:b337063899 . _:b337064590 . . _:b337063936 . _:b337063914 . . _:b337064524 . . _:b337063458 . _:b337064180 . . . _:b337063644 . . _:b337063788 . . . . . _:b337064625 . . . _:b337064055 . . . . . . _:b337064471 . _:b337064048 . _:b337064543 . _:b337063441 . _:b337064426 . _:b337063626 . . . _:b337063979 . _:b337064112 . _:b337063716 . . . . . _:b337064628 . . . _:b337063961 . . _:b1842467 . . . _:b337063460 . . _:b337064445 . . . . _:b337063345 . . _:b337064158 . _:b337063477 . . . _:b337063790 . . . _:b337064382 . _:b337063430 "9"^^ . _:b337063753 . _:b337064651 . _:b337063431 "9"^^ . _:b337063941 . _:b337063428 "9"^^ . _:b337063429 "9"^^ . _:b337063426 "10"^^ . _:b337063427 "9"^^ . _:b337063944 . _:b337063425 "10"^^ . . _:b337063424 "10"^^ . . . _:b337063438 "9"^^ . _:b337064580 . _:b337063387 . _:b337064602 . . _:b337064279 . _:b337063439 "9"^^ . _:b337063436 "9"^^ . . _:b337063437 "9"^^ . . . . _:b337063434 "9"^^ . _:b337063435 "9"^^ . _:b337063432 "9"^^ . _:b337064338 . _:b337063433 "9"^^ . _:b337063446 "9"^^ . _:b337063447 "8"^^ . . _:b337063444 "9"^^ . . _:b337063332 . _:b337063445 "9"^^ . _:b337063442 "9"^^ . _:b337064627 . _:b337063443 "9"^^ . _:b337063440 "9"^^ . _:b337064082 . _:b337063441 "9"^^ . _:b337063443 . _:b337063454 "8"^^ . . . _:b337064185 . _:b337063455 "8"^^ . _:b337063512 . _:b337063452 "8"^^ . _:b337063453 "8"^^ . _:b337063450 "8"^^ . _:b337064333 . _:b337063451 "8"^^ . . _:b337063448 "8"^^ . . . _:b337063449 "8"^^ . _:b1842431 "introduction" . _:b337063462 "8"^^ . _:b337064046 . _:b337063463 "8"^^ . _:b337063460 "8"^^ . _:b337063461 "8"^^ . _:b337064583 . . _:b337063458 "8"^^ . _:b337063459 "8"^^ . . _:b337063456 "8"^^ . _:b337063457 "8"^^ . . _:b337063470 "8"^^ . _:b337063471 "8"^^ . _:b337063468 "8"^^ . _:b337063469 "8"^^ . . . _:b337063466 "8"^^ . _:b337063909 . _:b337063467 "8"^^ . . _:b337063464 "8"^^ . _:b337063465 "8"^^ . . _:b337063478 "7"^^ . . . _:b337064194 . _:b337063479 "7"^^ . . _:b337063476 "7"^^ . . . _:b337063477 "7"^^ . . _:b337063569 . . _:b337063474 "8"^^ . _:b337063773 . _:b337063475 "8"^^ . _:b337064607 . _:b337063733 . _:b337063591 . _:b337063472 "8"^^ . . _:b337063473 "8"^^ . _:b337063486 "7"^^ . . . _:b337063487 "7"^^ . _:b337064638 . _:b337064135 . _:b337063484 "7"^^ . _:b337064540 . _:b337063485 "7"^^ . . . _:b337063482 "7"^^ . _:b337063483 "7"^^ . _:b337063480 "7"^^ . . _:b337064006 . . _:b337063481 "7"^^ . _:b337063494 "7"^^ . _:b337064223 . . _:b337064419 . _:b337063495 "7"^^ . . . _:b337063652 . _:b337063492 "7"^^ . _:b337063493 "7"^^ . _:b337063490 "7"^^ . _:b337063491 "7"^^ . _:b337063985 . _:b337063488 "7"^^ . _:b337063489 "7"^^ . . . . _:b337064268 . _:b337063502 "7"^^ . _:b337063503 "7"^^ . . _:b337063500 "7"^^ . _:b337063501 "7"^^ . _:b337064621 . _:b337063498 "7"^^ . . _:b337063499 "7"^^ . _:b337063496 "7"^^ . _:b337063537 . . _:b337063497 "7"^^ . _:b337063510 "6"^^ . _:b337063511 "6"^^ . _:b337063508 "6"^^ . _:b337063509 "6"^^ . _:b337063506 "6"^^ . _:b337063507 "6"^^ . . _:b337063504 "6"^^ . _:b337063505 "6"^^ . _:b337063518 "6"^^ . _:b337063519 "6"^^ . _:b337063516 "6"^^ . _:b337063517 "6"^^ . _:b337063514 "6"^^ . _:b337063515 "6"^^ . _:b337063980 . _:b337063512 "6"^^ . _:b337063513 "6"^^ . . _:b337063526 "6"^^ . _:b337063700 . _:b337063527 "6"^^ . . _:b337063524 "6"^^ . . _:b337063525 "6"^^ . _:b337064225 . . _:b337063522 "6"^^ . . . . _:b337063523 "6"^^ . _:b337063520 "6"^^ . _:b337063745 . _:b337063718 . _:b337063521 "6"^^ . . . _:b337063534 "6"^^ . _:b1842476 "3; Liou et al., 2005; Zhang et al., >>2005<<) and confirm that the N terminus of STIM1 faces the ER lumen." . . _:b337063535 "6"^^ . . _:b337063532 "6"^^ . _:b337063962 . . _:b337063533 "6"^^ . . . _:b337063530 "6"^^ . . _:b337063418 . _:b337063531 "6"^^ . _:b337064261 . _:b337063928 . _:b337063528 "6"^^ . . _:b337064378 . _:b337064148 . _:b337063529 "6"^^ . . _:b337063743 . _:b337063542 "6"^^ . . _:b337063543 "6"^^ . _:b337063344 . . _:b337063540 "6"^^ . _:b337063541 "6"^^ . _:b337063538 "6"^^ . _:b337063539 "6"^^ . _:b337063536 "6"^^ . _:b337063889 . _:b337063537 "6"^^ . _:b337063549 "5"^^ . . _:b337063548 "5"^^ . _:b337063562 . _:b337063551 "5"^^ . . _:b337063550 "5"^^ . _:b337063802 . _:b337063905 . _:b337063544 "6"^^ . . _:b337063547 "5"^^ . _:b337063545 "6"^^ . _:b337063546 "5"^^ . . . _:b337063557 "5"^^ . _:b337063394 . _:b337063556 "5"^^ . _:b337063559 "5"^^ . . _:b337063558 "5"^^ . . _:b337063553 "5"^^ . . _:b337064266 . _:b337063552 "5"^^ . _:b337064588 . _:b337063555 "5"^^ . . _:b337063554 "5"^^ . _:b337063882 . . _:b337063565 "5"^^ . _:b337063564 "5"^^ . _:b337064484 . _:b337064013 . _:b337063567 "5"^^ . _:b337063566 "5"^^ . _:b337064636 . _:b337063561 "5"^^ . _:b337063560 "5"^^ . . _:b337063563 "5"^^ . . _:b337063562 "5"^^ . _:b337064104 . _:b337063573 "5"^^ . _:b337063572 "5"^^ . _:b337063575 "5"^^ . . . _:b337063574 "5"^^ . _:b337063569 "5"^^ . _:b337063656 . "10.1083%2Fjcb.200604014" . _:b337063568 "5"^^ . . . _:b337063586 . _:b337063484 . _:b337063571 "5"^^ . . . _:b337063570 "5"^^ . . _:b337064642 . _:b337063706 . . _:b337063737 . _:b337063581 "5"^^ . _:b337064136 . _:b337063580 "5"^^ . _:b337063583 "5"^^ . . _:b337063582 "5"^^ . _:b337063577 "5"^^ . _:b337063947 . . _:b337063559 . _:b337063576 "5"^^ . . _:b337063579 "5"^^ . _:b337063553 . . _:b337063578 "5"^^ . _:b337064205 . . _:b337063589 "5"^^ . . . . _:b337063588 "5"^^ . _:b337063591 "5"^^ . _:b337064121 . _:b337064420 . _:b337064449 . _:b337063590 "5"^^ . _:b1842434 "a critical role in promoting gene expression during T cell activation, as shown by spontaneous mutations that abrogate Ca2+ influx and cause severe combined immunodeficiency in human patients (Partiseti et al., 1994; Feske et al., >>2005<<, 2006)." . _:b337063585 "5"^^ . _:b337063489 . _:b337063584 "5"^^ . . _:b337063587 "5"^^ . _:b337063973 . _:b337063586 "5"^^ . . . _:b337063597 "5"^^ . . _:b337063596 "5"^^ . . _:b337063678 . _:b337063599 "5"^^ . . _:b337064345 . . _:b337063819 . _:b337063598 "5"^^ . . _:b337063593 "5"^^ . _:b337063592 "5"^^ . _:b337063849 . _:b337064007 . _:b337064211 . . . _:b337063595 "5"^^ . . _:b337064361 . _:b337063594 "5"^^ . _:b337063605 "4"^^ . _:b337063604 "4"^^ . . . _:b337063607 "4"^^ . _:b337063606 "4"^^ . _:b337063893 . _:b337064253 . . _:b337063601 "5"^^ . _:b337063413 . . . _:b337063600 "5"^^ . _:b337063603 "4"^^ . . . _:b337063602 "5"^^ . . _:b337063613 "4"^^ . _:b337063612 "4"^^ . _:b337063615 "4"^^ . . _:b337063431 . . _:b337063614 "4"^^ . _:b337063609 "4"^^ . _:b337064626 . . _:b337064639 . _:b337063608 "4"^^ . . _:b337063611 "4"^^ . _:b337064251 . . _:b337063610 "4"^^ . . _:b337063621 "4"^^ . . _:b337063620 "4"^^ . . _:b337063623 "4"^^ . _:b337063389 . _:b337063622 "4"^^ . _:b337063601 . _:b337063617 "4"^^ . . . _:b337063646 . _:b337063616 "4"^^ . _:b337063619 "4"^^ . _:b337063950 . _:b337063618 "4"^^ . _:b337063892 . _:b337063629 "4"^^ . . . . _:b337063628 "4"^^ . _:b337063631 "4"^^ . _:b337063630 "4"^^ . . _:b337064423 . _:b337064058 . _:b337063625 "4"^^ . _:b337063841 . _:b337063624 "4"^^ . _:b337063627 "4"^^ . _:b337063626 "4"^^ . _:b337063524 . _:b337064649 . _:b337063637 "4"^^ . . _:b337063636 "4"^^ . . . _:b1842431 . _:b337064217 . _:b337063639 "4"^^ . . _:b337063638 "4"^^ . _:b337064558 . _:b337063633 "4"^^ . _:b337063758 . _:b337063632 "4"^^ . . _:b337063635 "4"^^ . _:b337063634 "4"^^ . _:b337063645 "4"^^ . _:b337064089 . _:b337063644 "4"^^ . _:b337063647 "4"^^ . _:b337063646 "4"^^ . _:b337063641 "4"^^ . . _:b337063712 . _:b337063640 "4"^^ . _:b1842443 "First, STIM1 molecules bearing EF-hand mutations are constitutively localized in these puncta, even when stores are full, consistent with their ability to constitutively activate Ca2+ entry (Liou et al., 2005; Zhang et al., >>2005<<). Second, redistribution brings STIM1 toward the plasma membrane, suggesting a means by which STIM1 could transmit a store depletion signal to CRAC channels." . _:b337063643 "4"^^ . _:b337064332 . . _:b337063642 "4"^^ . . _:b337063653 "4"^^ . . . . _:b337063652 "4"^^ . _:b337063693 . _:b337063335 . _:b337063406 . _:b337063655 "4"^^ . . _:b337063654 "4"^^ . _:b337063649 "4"^^ . _:b337064341 . _:b337063648 "4"^^ . _:b337064348 . _:b337063651 "4"^^ . _:b337063650 "4"^^ . _:b337063661 "4"^^ . . _:b337063660 "4"^^ . . . _:b337063663 "4"^^ . _:b337063662 "4"^^ . _:b337063657 "4"^^ . . . _:b337063656 "4"^^ . _:b337063605 . . _:b337063659 "4"^^ . _:b337063374 . _:b337063658 "4"^^ . _:b337063669 "4"^^ . _:b337064004 . _:b337063668 "4"^^ . _:b337063671 "4"^^ . _:b337063468 . _:b337064360 . . _:b337063670 "4"^^ . . _:b337064393 . _:b337063572 . _:b337063665 "4"^^ . _:b337063664 "4"^^ . . _:b337063667 "4"^^ . . _:b337064034 . _:b337063666 "4"^^ . _:b337063677 "4"^^ . . _:b337064219 . _:b337063676 "4"^^ . _:b337063679 "4"^^ . . . _:b337063678 "4"^^ . _:b337063673 "4"^^ . . _:b337063672 "4"^^ . . _:b337063675 "4"^^ . _:b337064002 . _:b337063763 . _:b337063674 "4"^^ . _:b337063685 "4"^^ . _:b337063684 "4"^^ . . _:b337063514 . . _:b337063687 "4"^^ . _:b337063686 "4"^^ . _:b337063681 "4"^^ . _:b337064584 . . _:b337063680 "4"^^ . _:b337064606 . . _:b337063724 . _:b337063683 "4"^^ . _:b337063682 "4"^^ . . _:b337063693 "4"^^ . _:b337063692 "4"^^ . _:b337064402 . _:b337064389 . _:b337064531 . _:b337064379 . _:b337063695 "4"^^ . _:b337063694 "4"^^ . _:b337064316 . . _:b337063689 "4"^^ . _:b337063688 "4"^^ . _:b337063650 . . . _:b337063691 "4"^^ . _:b337063690 "4"^^ . _:b337063701 "4"^^ . . _:b337063700 "4"^^ . _:b337063703 "4"^^ . _:b337063702 "4"^^ . _:b337063697 "4"^^ . _:b337063696 "4"^^ . _:b337063699 "4"^^ . _:b337063698 "4"^^ . _:b337064481 . _:b337063795 . _:b337063709 "4"^^ . . _:b337063708 "4"^^ . _:b337064363 . . _:b337063711 "4"^^ . _:b337063410 . _:b337063710 "4"^^ . _:b337063336 . _:b337064557 . _:b337063705 "4"^^ . . . _:b337063704 "4"^^ . _:b337064020 . _:b337063707 "4"^^ . _:b337063617 . _:b1842437 "Despite persistent research efforts over the past 15 yr, there is still a lack of consensus as to the molecular mechanism underlying store-operated Ca2+ entry (for reviews see Venkatachalam et al., 2002; Parekh and Putney, >>2005<<). A major stumbling block in this search has been the lack of identified proteins that could be shown to be unequivocally required for the process." . _:b337063706 "4"^^ . . _:b337063717 "4"^^ . . _:b337064436 . _:b337064181 . _:b337063716 "4"^^ . _:b337063886 . _:b337063719 "4"^^ . . _:b337063718 "4"^^ . _:b337064546 . . _:b337063713 "4"^^ . . . _:b337063712 "4"^^ . . _:b337064421 . _:b337063715 "4"^^ . . _:b337063714 "4"^^ . . _:b337063725 "3"^^ . . _:b337064474 . _:b337063724 "3"^^ . _:b337063794 . _:b337063727 "3"^^ . _:b337063847 . _:b337063726 "3"^^ . _:b337064032 . _:b337063721 "4"^^ . . _:b337063720 "4"^^ . _:b337063723 "3"^^ . . _:b337064403 . _:b337063722 "4"^^ . _:b337064563 . _:b337063733 "3"^^ . _:b337064303 . _:b337063732 "3"^^ . _:b337063567 . _:b337063749 . _:b337063735 "3"^^ . . _:b337063734 "3"^^ . _:b337063705 . _:b337063729 "3"^^ . . _:b337063728 "3"^^ . _:b337064035 . _:b337063610 . . _:b337063731 "3"^^ . . . _:b337063730 "3"^^ . . _:b337063741 "3"^^ . . _:b337063740 "3"^^ . _:b337064096 . _:b337063743 "3"^^ . . _:b337063500 . . _:b337063742 "3"^^ . _:b337063737 "3"^^ . _:b337064497 . _:b337063736 "3"^^ . _:b337063739 "3"^^ . . . _:b337063738 "3"^^ . _:b337064619 . . _:b337063749 "3"^^ . _:b337063731 . _:b337063823 . _:b337063748 "3"^^ . . . _:b337064053 . _:b337063628 . _:b337063751 "3"^^ . _:b337063877 . _:b337063750 "3"^^ . _:b337063745 "3"^^ . _:b337063531 . . _:b337063744 "3"^^ . _:b337063747 "3"^^ . _:b337063989 . _:b337064516 . . _:b337063746 "3"^^ . _:b337064215 . _:b337063757 "3"^^ . . . _:b337063756 "3"^^ . . _:b337063759 "3"^^ . . _:b337064011 . _:b337064412 . _:b337063758 "3"^^ . . _:b337064242 . _:b1842509 . _:b337063753 "3"^^ . _:b337064124 . _:b337063752 "3"^^ . . _:b337064238 . . _:b337063755 "3"^^ . _:b337063482 . _:b337063754 "3"^^ . _:b337063748 . . _:b337063765 "3"^^ . . . _:b337063764 "3"^^ . _:b337063767 "3"^^ . . . _:b337063766 "3"^^ . _:b337063761 "3"^^ . . . _:b337063760 "3"^^ . _:b337063763 "3"^^ . . _:b337063762 "3"^^ . _:b337063383 . _:b337064505 . _:b337063773 "3"^^ . . . . _:b337063772 "3"^^ . _:b337063775 "3"^^ . _:b337063663 . _:b337063969 . _:b337063774 "3"^^ . . _:b337063769 "3"^^ . _:b337064184 . _:b337063660 . _:b337063768 "3"^^ . _:b337063370 . _:b337063771 "3"^^ . _:b337063770 "3"^^ . . _:b337063781 "3"^^ . _:b337063927 . _:b337064350 . _:b337063780 "3"^^ . _:b1842473 "fusion proteins in the ER, Golgi, and transport vesicles has been achieved with very high contrast and without permeabilization, using peroxidase cytochemistry and conventional transmission EM (Connolly et al., 1994; Dubois et al., >>2001<<). Because the HRP reaction product is restricted to the lumen of the HRP-containing compartment, ER-localized STIM1 should be clearly distinguishable from STIM1 in the plasma membrane." . . _:b337063783 "3"^^ . . . _:b337063782 "3"^^ . . _:b337063777 "3"^^ . _:b337063775 . _:b337063776 "3"^^ . _:b337063779 "3"^^ . . . _:b337063778 "3"^^ . _:b337064601 . _:b337063789 "3"^^ . _:b337063788 "3"^^ . _:b337063791 "3"^^ . _:b337063790 "3"^^ . _:b337063785 "3"^^ . _:b337063784 "3"^^ . _:b337063787 "3"^^ . . _:b337063519 . _:b337063786 "3"^^ . _:b1842505 . _:b337064572 . _:b337063797 "3"^^ . _:b337063796 "3"^^ . _:b337064033 . _:b1842458 "results" . _:b337063799 "3"^^ . . _:b337063798 "3"^^ . _:b337063793 "3"^^ . _:b337064305 . _:b337063792 "3"^^ . _:b337064493 . _:b337063795 "3"^^ . . . _:b337063794 "3"^^ . . _:b337063805 "3"^^ . _:b337063904 . _:b337063804 "3"^^ . . _:b337063880 . _:b337063859 . _:b337063807 "3"^^ . _:b337063806 "3"^^ . _:b337063801 "3"^^ . _:b337063800 "3"^^ . _:b337063803 "3"^^ . _:b337063948 . _:b337063802 "3"^^ . _:b337063813 "3"^^ . . _:b337063812 "3"^^ . _:b337063428 . _:b337063815 "3"^^ . . . _:b337063814 "3"^^ . _:b337063809 "3"^^ . _:b337064545 . . _:b337063808 "3"^^ . _:b1842440 "STIM1 has an EF-hand domain predicted to face the ER lumen, and mutations of residues that are expected to reduce STIM1's affinity for Ca2+ constitutively activate store-operated Ca2+ entry in cells with full Ca2+ stores (Liou et al., >>2005<<; Zhang et al., 2005). Interestingly, store depletion causes wild-type STIM1 to redistribute from a diffuse ER localization into puncta located at the cell periphery." . _:b337063811 "3"^^ . _:b337063555 . _:b337063810 "3"^^ . . _:b337063821 "3"^^ . _:b337064182 . _:b337063820 "3"^^ . _:b337063823 "3"^^ . _:b337063870 . _:b337063822 "3"^^ . _:b337063817 "3"^^ . . _:b337063838 . _:b337063616 . _:b337063816 "3"^^ . . _:b337063819 "3"^^ . _:b337064428 . _:b337064304 . _:b337063818 "3"^^ . _:b337063945 . _:b337063829 "3"^^ . _:b337064488 . _:b337063792 . . . _:b337064222 . _:b337063828 "3"^^ . _:b337063719 . _:b337063831 "3"^^ . _:b337063830 "3"^^ . _:b337063825 "3"^^ . _:b337063824 "3"^^ . _:b337063827 "3"^^ . . . _:b337063826 "3"^^ . . _:b337063837 "3"^^ . . _:b337063836 "3"^^ . . . _:b337063839 "3"^^ . _:b337064331 . . . _:b337063838 "3"^^ . . _:b337063833 "3"^^ . . _:b337063832 "3"^^ . _:b337063835 "3"^^ . _:b337063632 . _:b337064489 . _:b337063834 "3"^^ . . _:b337063625 . _:b337064145 . _:b337063845 "3"^^ . _:b337063714 . _:b337063844 "3"^^ . _:b337063847 "3"^^ . _:b337063846 "3"^^ . _:b337064116 . . _:b337063841 "3"^^ . . _:b337063840 "3"^^ . _:b337063843 "3"^^ . _:b337063506 . _:b337063842 "3"^^ . _:b337064465 . . _:b337063853 "3"^^ . . _:b337063852 "3"^^ . _:b337063855 "3"^^ . _:b337063854 "3"^^ . . . _:b337063849 "3"^^ . . . _:b337063848 "3"^^ . _:b337063565 . _:b337063699 . _:b337063851 "3"^^ . _:b337064025 . . . _:b337063850 "3"^^ . _:b337063798 . _:b337063861 "3"^^ . _:b337063330 . _:b337063860 "3"^^ . _:b337063863 "3"^^ . . _:b337063862 "3"^^ . _:b337063857 "3"^^ . . _:b337063912 . . _:b337063856 "3"^^ . _:b337063631 . _:b337063828 . _:b337063859 "3"^^ . . _:b337063858 "3"^^ . . _:b337063869 "3"^^ . _:b337063774 . . . _:b337063868 "3"^^ . _:b337063457 . _:b337063871 "3"^^ . _:b337063750 . . . _:b337063870 "3"^^ . . _:b337063865 "3"^^ . _:b337063342 . _:b337063574 . _:b337063864 "3"^^ . . _:b337063867 "3"^^ . . _:b337063541 . . _:b337063866 "3"^^ . _:b337063877 "3"^^ . _:b337063725 . . . _:b337063876 "3"^^ . _:b337064609 . _:b337063879 "3"^^ . _:b337063878 "3"^^ . . . _:b337063873 "3"^^ . . . _:b337063872 "3"^^ . _:b337063875 "3"^^ . _:b337063874 "3"^^ . _:b337063462 . _:b337063885 "3"^^ . _:b337063884 "3"^^ . . . . _:b337063887 "3"^^ . _:b337063886 "3"^^ . _:b337064153 . . _:b337063881 "3"^^ . _:b337063880 "3"^^ . _:b337063883 "3"^^ . _:b337064555 . _:b337063688 . _:b337064128 . _:b337063882 "3"^^ . _:b337063893 "3"^^ . _:b1842511 . _:b337063426 . _:b337063892 "3"^^ . _:b337063895 "3"^^ . _:b337063627 . . _:b337063894 "3"^^ . _:b337063338 . . . _:b337063889 "3"^^ . _:b337063939 . _:b337063888 "3"^^ . . _:b337063891 "3"^^ . _:b337063972 . _:b337064351 . _:b337063890 "3"^^ . . _:b337063901 "3"^^ . . _:b337063900 "3"^^ . . . _:b337063903 "3"^^ . _:b337064359 . _:b337063902 "3"^^ . _:b337063615 . _:b337063958 . _:b337063897 "3"^^ . . _:b337063623 . _:b337063896 "3"^^ . . . _:b337063899 "3"^^ . . _:b337063898 "3"^^ . _:b337063909 "3"^^ . _:b337064339 . _:b337063835 . _:b337064229 . _:b337063908 "3"^^ . . _:b1842473 . _:b337063911 "3"^^ . _:b337063674 . _:b337063910 "3"^^ . _:b337063905 "3"^^ . _:b337063904 "3"^^ . _:b337064015 . _:b337063907 "3"^^ . _:b1842496 "There is evidence for STIM1 expression in the plasma membrane based on immunolabeling and biotinylation of K562 cells, although the same caveats about biotinylation apply to this study (Manji et al., >>2000<<). It is important to note, however, that although some STIM1 may be expressed at the cell surface, our results show no detectable insertion of STIM1 into the plasma membrane on the time scale of CRAC channel opening, making it unlikely" . _:b1842452 . _:b337063906 "3"^^ . . _:b337063911 . . _:b337063917 "3"^^ . . _:b337063916 "3"^^ . _:b337064068 . _:b337063919 "3"^^ . _:b337063918 "3"^^ . _:b337063913 "3"^^ . _:b337063912 "3"^^ . . _:b337063915 "3"^^ . . _:b337063914 "3"^^ . _:b337063518 . _:b337063925 "3"^^ . _:b337064276 . _:b337063924 "3"^^ . . _:b337064616 . _:b337063927 "3"^^ . . _:b337063926 "3"^^ . _:b337063921 "3"^^ . . _:b337063920 "3"^^ . _:b337063923 "3"^^ . _:b337064191 . _:b337063922 "3"^^ . _:b337063933 "3"^^ . . _:b337064200 . _:b337064270 . _:b337063932 "3"^^ . _:b337063844 . _:b337063935 "3"^^ . _:b337063934 "3"^^ . . . _:b337063929 "3"^^ . _:b337063928 "3"^^ . _:b337063931 "3"^^ . . _:b1842459 "measured in cell populations has been shown to occur on average with roughly the same time course as CRAC channel activation, a direct comparison of STIM1 puncta formation and ICRAC activation has not been done (Liou et al., >>2005<<; Zhang et al., 2005). If the formation of STIM1 puncta is necessary for CRAC channel activation, it must precede channel opening." . _:b337063930 "3"^^ . _:b337063576 . . _:b337064618 . _:b337063984 . . _:b337064247 . _:b337063786 . _:b337063403 . . _:b337063696 . . . _:b337063639 . . . _:b337063649 . _:b337064317 . _:b337064541 . _:b337064080 . . _:b337063378 . . . _:b337064212 . _:b337063547 . _:b337063829 . . _:b337063471 . _:b337063542 . . . _:b337064605 . _:b1842510 . _:b337064231 . _:b1842436 "Despite persistent research efforts over the past 15 yr, there is still a lack of consensus as to the molecular mechanism underlying store-operated Ca2+ entry (for reviews see Venkatachalam et al., >>2002<<; Parekh and Putney, 2005). A major stumbling block in this search has been the lack of identified proteins that could be shown to be unequivocally required for the process." . . _:b337063333 . _:b1842496 . _:b337063606 . _:b337063528 . _:b337064581 . _:b337064119 . . . . _:b337063873 . _:b337064608 . _:b337064059 . . _:b337064120 . . _:b337064066 . . _:b337063875 . _:b337063953 . . _:b337063715 . . . _:b337064179 . _:b337063637 . . . _:b337064097 . _:b337064103 . . _:b337064074 . . _:b337063510 . . . . . _:b337063779 . _:b337064183 . . _:b337064335 . _:b337064453 "2"^^ . _:b337064452 "2"^^ . _:b337064455 "2"^^ . . . _:b337064454 "2"^^ . . _:b337064449 "2"^^ . . _:b337064448 "2"^^ . _:b337064264 . _:b337063924 . _:b337064451 "2"^^ . _:b337064450 "2"^^ . . _:b337064461 "2"^^ . _:b337064460 "2"^^ . _:b337063349 . . _:b337064463 "2"^^ . _:b337064462 "2"^^ . . _:b337064457 "2"^^ . _:b337064553 . _:b337064456 "2"^^ . . . _:b337064459 "2"^^ . _:b337064458 "2"^^ . _:b337064469 "2"^^ . _:b337064468 "2"^^ . _:b337064471 "2"^^ . _:b337063755 . . . _:b337064470 "2"^^ . . _:b337063683 . _:b1842444 . _:b337064465 "2"^^ . . _:b337064464 "2"^^ . _:b1842446 . _:b337064467 "2"^^ . _:b337064269 . . _:b337064466 "2"^^ . . _:b1842440 . _:b337064477 "2"^^ . . . . . _:b337064476 "2"^^ . _:b1842442 . _:b337064479 "2"^^ . _:b337064479 . _:b1842513 "Studies detailed in Luik et al. (>>2006<<) address the functional aspects of this structure and define in detail its spatial relationship to open CRAC channels." . . _:b337064478 "2"^^ . _:b337064473 "2"^^ . _:b337064472 "2"^^ . _:b1842438 . _:b337064475 "2"^^ . . _:b337064474 "2"^^ . . _:b337064227 . _:b337064343 . _:b337064485 "2"^^ . _:b337064484 "2"^^ . _:b337064127 . _:b337063436 . _:b337064487 "2"^^ . _:b337064486 "2"^^ . . _:b337064481 "2"^^ . . _:b1842461 . _:b337064480 "2"^^ . _:b337064483 "2"^^ . _:b337064399 . _:b1842463 . _:b337064482 "2"^^ . . _:b337064493 "2"^^ . _:b337063851 . _:b337064492 "2"^^ . . _:b337064495 "2"^^ . _:b1842459 . _:b337063898 . _:b337064494 "2"^^ . _:b337064489 "2"^^ . _:b337064488 "2"^^ . _:b337063481 . _:b337064491 "2"^^ . . _:b337064490 "2"^^ . _:b337064631 . . _:b337063464 . _:b337064501 "2"^^ . . _:b337063978 . _:b337064500 "2"^^ . _:b337063685 . . _:b337063685 . . _:b337064611 . _:b337064450 . _:b337064503 "2"^^ . _:b337063684 . . _:b1842432 "binding to the T cell receptor (TCR) elevates inositol 1,4,5-trisphosphate (IP3), depleting intracellular Ca2+ stores and thereby activating a highly Ca2+-selective SOC called the Ca2+ release\u2013activated Ca2+ (CRAC) channel (Lewis, >>2001<<). CRAC channels play a critical role in promoting gene expression during T cell activation, as shown by spontaneous mutations that abrogate Ca2+ influx and cause severe combined immunodeficiency in human patients (Partiseti et al., 1994;" . . _:b337064502 "2"^^ . _:b337063687 . _:b337064497 "2"^^ . _:b337063686 . _:b337064496 "2"^^ . _:b337063681 . . _:b337064499 "2"^^ . _:b337063680 . _:b337064498 "2"^^ . _:b337063683 . _:b337064509 "2"^^ . _:b337063682 . _:b337064508 "2"^^ . _:b337063693 . _:b337064511 "2"^^ . _:b337063692 . . _:b1842475 . _:b337064510 "2"^^ . _:b337063695 . _:b337064218 . _:b337064417 . . _:b1842468 . _:b337063955 . _:b337064505 "2"^^ . . . _:b337063694 . _:b337063734 . . . _:b337063991 . _:b337064504 "2"^^ . _:b337063689 . _:b337064507 "2"^^ . _:b337064604 . _:b337063688 . _:b337064506 "2"^^ . _:b337063691 . _:b337064383 . _:b337064517 "2"^^ . _:b337063690 . _:b337064346 . _:b337064516 "2"^^ . _:b337063701 . _:b337064519 "2"^^ . . _:b337063700 . _:b337064023 . _:b337064518 "2"^^ . _:b337063703 . . _:b1842480 "In terms of width and proximity to the plasma membrane, these ER\u2013plasma membrane contact sites resemble the \u201Cjunctional ER\u201D described in many cell types (Gardiner and Grey, 1983; Takeshima et al., 2000; Baumann and Walz, 2001; Levine, >>2004<<). The presence of junctional ER in resting Jurkat cells raises the question of whether STIM1 puncta form at these preexisting sites of ER\u2013plasma membrane contact." . _:b337063990 . _:b337064513 "2"^^ . _:b337063702 . . . _:b337064425 . _:b337064512 "2"^^ . _:b337063697 . . _:b337064515 "2"^^ . _:b337063696 . _:b337064514 "2"^^ . _:b337063699 . _:b1842488 . _:b337064525 "2"^^ . _:b337063698 . _:b337064524 "2"^^ . _:b337063709 . _:b337064230 . _:b337064527 "2"^^ . _:b337063708 . . _:b337063594 . _:b337064526 "2"^^ . _:b337064560 . _:b337063711 . . _:b337064521 "2"^^ . _:b337063710 . _:b337064520 "2"^^ . _:b337063705 . . _:b337064523 "2"^^ . _:b337063704 . _:b337063525 . . . _:b337064522 "2"^^ . _:b337064579 . _:b337063707 . _:b337064533 "2"^^ . _:b337063706 . _:b337064532 "2"^^ . _:b337063717 . _:b337064469 . _:b337063831 . _:b337064535 "2"^^ . _:b337063716 . _:b1842483 . _:b337064534 "2"^^ . _:b337063719 . _:b337064529 "2"^^ . _:b337063718 . _:b337064528 "2"^^ . _:b337063713 . _:b337064531 "2"^^ . _:b337063712 . _:b337064530 "2"^^ . _:b337063715 . _:b337064541 "2"^^ . _:b337063714 . _:b337063986 . _:b337064540 "2"^^ . _:b337063725 . _:b337064543 "2"^^ . _:b337063724 . _:b337064542 "2"^^ . _:b337063727 . _:b337064537 "2"^^ . _:b337063726 . _:b337064536 "2"^^ . _:b337063721 . _:b337064220 . _:b337064366 . _:b337064539 "2"^^ . _:b337063720 . _:b337064538 "2"^^ . _:b337063723 . _:b337064549 "2"^^ . _:b337063722 . . _:b337064548 "2"^^ . _:b337063733 . _:b337064018 . _:b337064551 "2"^^ . _:b337063732 . . _:b337064550 "2"^^ . _:b337063735 . _:b337064111 . _:b337064545 "2"^^ . _:b337063734 . _:b337064544 "2"^^ . _:b337063729 . . _:b337064547 "2"^^ . _:b337063728 . _:b337064546 "2"^^ . _:b337063731 . . . _:b337064557 "2"^^ . _:b337063730 . _:b337064556 "2"^^ . _:b337063741 . . _:b337064559 "2"^^ . _:b337063740 . . _:b337063451 . _:b337064558 "2"^^ . _:b337063743 . _:b337064630 . _:b337063720 . . _:b337064553 "2"^^ . _:b337063742 . _:b337064552 "2"^^ . _:b337063737 . _:b337063377 . _:b337064555 "2"^^ . _:b337063736 . _:b337064554 "2"^^ . _:b337063739 . _:b337064565 "2"^^ . _:b337063641 . _:b337063738 . _:b337064564 "2"^^ . _:b337063749 . . _:b337064567 "2"^^ . _:b337063748 . _:b337063633 . _:b337064566 "2"^^ . _:b337063751 . . _:b337064561 "2"^^ . _:b337063750 . _:b337064560 "2"^^ . _:b337063745 . _:b337064440 . _:b337064563 "2"^^ . _:b337063744 . . . _:b337064562 "2"^^ . _:b337063747 . _:b337064573 "2"^^ . _:b337063746 . _:b337064572 "2"^^ . _:b337063757 . . _:b337064575 "2"^^ . _:b337063756 . . _:b337064574 "2"^^ . _:b337063759 . . _:b337064569 "2"^^ . _:b337063758 . _:b337063448 . . _:b337064568 "2"^^ . _:b337063753 . _:b337064076 . _:b337064571 "2"^^ . _:b337063752 . _:b337064570 "2"^^ . _:b1842438 "In a major advance, two groups recently used RNAi-based screens to identify stromal interacting molecule 1 (STIM1) as an essential, conserved regulator of store-operated Ca2+ entry (Liou et al., >>2005<<; Roos et al., 2005)." . _:b337063755 . . _:b337064581 "2"^^ . _:b337063754 . _:b337064580 "2"^^ . _:b337063765 . _:b337063736 . _:b337064583 "2"^^ . _:b337063764 . _:b337064582 "2"^^ . _:b337063767 . _:b337064022 . _:b1842468 "3, A\u2013C), consistent with previous work (Liou et al., >>2005<<; Zhang et al., 2005). After store depletion, GFP-STIM1 accumulated in puncta close to the plasma membrane (Fig." . _:b337064577 "2"^^ . _:b337063766 . . _:b337064576 "2"^^ . _:b337063761 . . . _:b337064579 "2"^^ . _:b337063760 . _:b337063402 . _:b337063920 . . _:b337063568 . _:b337064578 "2"^^ . _:b337063763 . _:b337064589 "2"^^ . _:b337063762 . _:b337063513 . _:b337064588 "2"^^ . _:b337063773 . _:b1842494 . _:b337064591 "2"^^ . _:b337063772 . _:b337064375 . . _:b337064590 "2"^^ . _:b337063775 . _:b337064585 "2"^^ . _:b337063774 . . . _:b337064584 "2"^^ . _:b337064012 . _:b337063769 . _:b337064587 "2"^^ . _:b337063768 . _:b337064586 "2"^^ . . _:b337063771 . _:b337063803 . _:b337064597 "2"^^ . . _:b337063770 . _:b337063921 . _:b337064596 "2"^^ . _:b337063781 . . _:b337064551 . _:b337064599 "2"^^ . _:b337063780 . . . _:b337064598 "2"^^ . _:b337063783 . _:b337064593 "2"^^ . _:b337063782 . _:b337064592 "2"^^ . _:b337063777 . . _:b337064595 "2"^^ . _:b337063776 . _:b337064594 "2"^^ . _:b337063779 . _:b337063900 . . _:b337064605 "2"^^ . _:b337063778 . _:b337064604 "2"^^ . _:b337063789 . _:b1842464 "As reported previously in intact cells (Liou et al., 2005; Zhang et al., >>2005<<), passive depletion of Ca2+ stores during whole-cell recording led to the appearance of GFP-STIM1 puncta near the plasma membrane (Fig." . _:b337064607 "2"^^ . _:b337063982 . _:b337063967 . _:b337063788 . _:b337063681 . _:b337064289 . _:b337064606 "2"^^ . _:b337063791 . _:b337064461 . _:b337063952 . _:b337064601 "2"^^ . _:b337063790 . _:b337064188 . _:b337064600 "2"^^ . _:b337063785 . . _:b337064603 "2"^^ . _:b337063784 . _:b337064602 "2"^^ . _:b337063787 . . _:b337064613 "2"^^ . _:b337063786 . . _:b1842501 . _:b337064612 "2"^^ . _:b337064272 . _:b337063797 . . _:b337064615 "2"^^ . _:b337063796 . _:b337063421 . _:b337064614 "2"^^ . _:b337063799 . _:b337064609 "2"^^ . _:b337063798 . _:b337063380 . _:b337064192 . _:b337064608 "2"^^ . _:b337063793 . _:b337064611 "2"^^ . _:b337063792 . _:b337064561 . . _:b337064610 "2"^^ . _:b337063795 . . _:b337064621 "2"^^ . _:b337064650 . _:b337063794 . . _:b337063337 . . _:b337064453 . _:b337064620 "2"^^ . . _:b337063805 . _:b337064452 . _:b337064623 "2"^^ . _:b337063804 . _:b337064455 . _:b337064530 . _:b337064622 "2"^^ . _:b337063807 . _:b337063933 . _:b337064454 . . _:b337064640 . _:b337064617 "2"^^ . _:b337063806 . _:b337064365 . _:b337064449 . _:b337063340 . _:b337064616 "2"^^ . _:b337063669 . _:b337063801 . _:b337064448 . _:b337064619 "2"^^ . _:b337063800 . _:b337064451 . _:b337064618 "2"^^ . _:b337063803 . _:b337064450 . _:b337064629 "2"^^ . _:b337063802 . _:b337064461 . _:b337064644 . _:b337064628 "2"^^ . _:b337063813 . _:b337064460 . _:b337063697 . _:b337064631 "2"^^ . _:b337063812 . _:b337064643 . _:b337064463 . . _:b337064630 "2"^^ . _:b337063535 . _:b337063815 . _:b337064462 . _:b337064625 "2"^^ . _:b337063814 . _:b337063966 . _:b337064457 . _:b1842506 . _:b337064624 "2"^^ . _:b337063809 . _:b1842511 "It is noteworthy that the cytoplasmic domain of STIM1 contains several putative protein interaction domains, including two \u03B1-helical coiled-coil domains and a proline-rich domain (Manji et al., 2000; Williams et al., >>2001<<). Proteins in opposing membrane compartments can form stable complexes through coiled-coil interactions; a classic example involves the SNARE proteins, which mediate vesicle docking and fusion through formation of a four-stranded" . _:b337064456 . _:b337064627 "2"^^ . _:b337063808 . _:b337064459 . . _:b337064626 "2"^^ . _:b337063811 . . _:b337063765 . _:b337064284 . . _:b337064458 . _:b337064637 "2"^^ . _:b337063810 . _:b337064469 . _:b337064636 "2"^^ . _:b337063821 . _:b337064468 . _:b337064639 "2"^^ . _:b337063820 . _:b337064471 . _:b337064638 "2"^^ . _:b337063823 . _:b337064470 . _:b337063784 . _:b337064633 "2"^^ . _:b337064254 . _:b337063822 . . _:b337064465 . _:b1842486 . _:b337064632 "2"^^ . _:b337063817 . _:b337064464 . _:b337064635 "2"^^ . _:b337063816 . _:b337064467 . _:b337064634 "2"^^ . _:b337063409 . _:b337063819 . _:b337064466 . _:b337064645 "2"^^ . _:b337063818 . _:b1842434 . _:b337064477 . _:b337063662 . _:b337064644 "2"^^ . _:b337063829 . . _:b337064476 . . _:b337064647 "2"^^ . . _:b337063828 . _:b337064479 . _:b1842442 "First, STIM1 molecules bearing EF-hand mutations are constitutively localized in these puncta, even when stores are full, consistent with their ability to constitutively activate Ca2+ entry (Liou et al., >>2005<<; Zhang et al., 2005)." . _:b337064646 "2"^^ . _:b337063831 . _:b337064042 . _:b337064478 . _:b337064641 "2"^^ . _:b337063830 . _:b337063837 . _:b337064473 . _:b337064640 "2"^^ . _:b337063825 . . _:b337064472 . _:b337064643 "2"^^ . _:b337063824 . _:b337064475 . _:b337064062 . _:b337064642 "2"^^ . _:b337063827 . _:b1842451 "HRP-labeled proteins have been used to study subcellular localization with greater spatial resolution and better preservation of membrane structure than is possible with immuno-EM (Connolly et al., >>1994<<; Dubois et al., 2001)." . . _:b337064474 . _:b337064653 "2"^^ . _:b337063826 . _:b337064485 . . _:b337064652 "2"^^ . _:b337064224 . _:b337063837 . _:b337064484 . _:b337064655 "2"^^ . _:b337063836 . _:b337064487 . . _:b337064654 "2"^^ . _:b337063839 . _:b337064486 . _:b337064649 "2"^^ . _:b337063838 . _:b337063598 . _:b337064481 . _:b337064648 "2"^^ . _:b337063833 . _:b337064527 . _:b337063721 . _:b337064480 . _:b337064651 "2"^^ . _:b337063832 . _:b337064483 . _:b337064650 "2"^^ . _:b337063835 . _:b337064482 . _:b337063834 . _:b337064493 . _:b337063845 . _:b337063935 . _:b337064492 . _:b337063844 . _:b337064522 . _:b337064495 . _:b1842477 . _:b337063847 . _:b337064494 . _:b337064657 "2"^^ . _:b337063846 . _:b337064489 . _:b337064656 "2"^^ . _:b337063841 . _:b337064328 . _:b337064488 . _:b337064477 . _:b337063728 . _:b337063840 . _:b337064491 . . _:b337064658 "2"^^ . _:b337063843 . _:b337064490 . _:b337063842 . _:b337064501 . _:b337063853 . _:b337064347 . _:b337064500 . _:b1842455 "Patch-clamp experiments were conducted in the standard whole-cell recording and perforated-patch configurations as previously described (Zweifach and Lewis, >>1995<<; Bautista et al., 2002). The internal solution for whole-cell recording contained 140 mM Cs aspartate, 3 mM MgCl2, 1 mM EGTA, and 10 mM Hepes, pH 7.2 with CsOH." . . . _:b1842433 . _:b337063852 . _:b337064503 . _:b337063855 . . _:b337064502 . _:b337063854 . _:b337063501 . _:b337064578 . _:b337064497 . _:b1842454 . _:b337063849 . _:b337064496 . _:b337064596 . _:b337063848 . _:b337064499 . . _:b337064190 . . _:b337063851 . _:b337064498 . . _:b337063850 . _:b337063673 . _:b337064509 . _:b337063861 . _:b337063770 . _:b337064508 . . _:b337063860 . . _:b337064511 . _:b337063863 . _:b337063630 . _:b337064510 . _:b337063862 . _:b337064505 . _:b337063857 . _:b1842499 . . _:b337064504 . . _:b337063856 . . _:b337064507 . _:b337063859 . _:b337064506 . _:b337063858 . _:b337064517 . _:b337063869 . _:b337064516 . _:b337063509 . _:b337063868 . _:b337063951 . _:b337064401 . _:b337064519 . . _:b337063871 . _:b337064518 . _:b337063870 . _:b337064513 . _:b337063865 . _:b337064512 . . _:b337063864 . _:b337064094 . _:b337064515 . _:b337063529 . . _:b337063867 . . _:b337064514 . . . _:b337063866 . _:b337064525 . _:b337063877 . _:b337063407 . _:b337064524 . _:b337063876 . . _:b337064527 . _:b337064467 . _:b337063879 . . _:b337063358 . _:b337064526 . _:b337063878 . . _:b337064400 . _:b337064521 . _:b337063873 . _:b337064520 . _:b1842498 . _:b337063872 . . _:b337064523 . _:b337063875 . _:b337064522 . _:b337063874 . _:b337064533 . _:b337064016 . _:b337063885 . . _:b337064532 . . _:b337063884 . _:b337064535 . . _:b337063887 . _:b337064534 . _:b337063886 . _:b337064529 . . _:b337063881 . . _:b337064528 . . _:b337063880 . . _:b337064531 . _:b337064504 . _:b337063883 . _:b337063908 . _:b337064530 . . _:b337063882 . . _:b337064541 . . _:b337063893 . . . _:b337064540 . _:b337063892 . _:b337064543 . _:b337063895 . _:b337064542 . _:b1842481 "discussion" . _:b337063894 . _:b337064177 . _:b337064537 . _:b337063889 . . _:b337064536 . _:b337063888 . _:b1842485 "and the dynamics of ER movement to the plasma membrane may limit the speed with which CRAC channels respond to changes in ER [Ca2+], which takes tens of seconds even in response to rapid IP3-induced Ca2+ release (Hoth and Penner, >>1993<<; Prakriya and Lewis, 2001)." . _:b337064539 . _:b337064466 . _:b337063891 . _:b337064009 . _:b337064538 . . _:b337063890 . _:b337064334 . _:b337064549 . _:b337063901 . _:b337064534 . . _:b337064548 . _:b337063900 . _:b337063812 . _:b337064551 . _:b337063903 . _:b1842465 "The mean density of ICRAC was increased by 78 \u00B1 30% (transfected, n = 6; control, n = 14) in cells expressing low to moderate levels of GFP-STIM1 (or Cherry-STIM1; Luik et al., >>2006<<), suggesting that the abundance of endogenous STIM1 may normally limit the extent of CRAC channel activation." . _:b337064550 . _:b337063902 . _:b337064545 . _:b337063897 . . _:b337064544 . _:b337063896 . . _:b337063968 . _:b337064547 . . . _:b337063899 . _:b337064546 . _:b337063898 . . . _:b337064557 . _:b337063909 . _:b337064556 . _:b337063908 . _:b337064559 . _:b337063911 . . . _:b337064558 . _:b337063910 . _:b337064553 . _:b337063905 . . _:b337064552 . _:b337063904 . . _:b337064555 . _:b337063907 . _:b337064198 . _:b337064554 . _:b337063906 . _:b337064565 . _:b337063917 . _:b337064564 . _:b337063916 . _:b337064567 . . _:b337063919 . _:b337064566 . _:b337063918 . _:b337064079 . _:b337064561 . _:b337063913 . . . _:b337064560 . . _:b337063912 . _:b337063495 . _:b337064563 . _:b337063796 . . _:b337063915 . . _:b337064562 . _:b337063983 . _:b337063914 . _:b337064573 . _:b337063507 . . _:b337063925 . . _:b337064572 . _:b337063924 . _:b337064575 . . _:b337063927 . _:b337064574 . _:b337063926 . _:b337064129 . _:b337064569 . _:b337063921 . . _:b337064568 . . _:b337063920 . . _:b337064571 . . . _:b337063923 . _:b337063360 . _:b337064570 . _:b337064337 . _:b337063922 . . . _:b337064581 . . _:b337063933 . . _:b337064580 . _:b337063932 . _:b337064583 . . _:b337063935 . _:b337064582 . _:b337063934 . . _:b337064577 . _:b337063929 . _:b337064576 . _:b337063928 . . _:b337064579 . _:b337063931 . . _:b337064578 . _:b1842487 . _:b337063930 . _:b337064496 . _:b337064589 . _:b337064637 . _:b337063429 . _:b337064588 . _:b337064040 . _:b337063428 . _:b337064178 . _:b337064591 . . _:b1842482 . _:b337063431 . . _:b337064513 . _:b337064590 . _:b337063430 . _:b337064585 . _:b1842435 "critical role in promoting gene expression during T cell activation, as shown by spontaneous mutations that abrogate Ca2+ influx and cause severe combined immunodeficiency in human patients (Partiseti et al., 1994; Feske et al., 2005, >>2006<<)." . _:b337063425 . _:b337064584 . _:b337063938 . _:b337063424 . _:b1842455 . _:b337064587 . _:b337063427 . _:b337064586 . _:b337063426 . _:b337064597 . _:b337063437 . _:b337063416 . _:b337064596 . _:b337063436 . . _:b337064599 . _:b337063439 . _:b337064598 . _:b337063438 . _:b337064593 . _:b337063433 . _:b337064592 . _:b337063432 . _:b337064595 . _:b337063557 . . _:b337063435 . _:b337063761 . _:b337064594 . _:b337063434 . _:b337064605 . _:b337063445 . _:b337064604 . . _:b1842465 . _:b337063444 . _:b337064607 . _:b337063895 . . _:b337064292 . _:b337063447 . _:b337064441 . _:b337064606 . . _:b337063446 . _:b337063603 . _:b337064601 . . _:b337063441 . . _:b337064600 . _:b337063440 . _:b337064603 . _:b337063443 . _:b337064602 . _:b337063442 . _:b1842478 . _:b337064613 . _:b337063453 . . _:b337063521 . _:b337064612 . _:b337063452 . _:b337064615 . . _:b337063455 . _:b337064614 . . _:b337064237 . _:b337063454 . _:b337064609 . _:b337064197 . _:b337063449 . _:b337064608 . _:b337063448 . _:b337064611 . _:b1842453 . _:b337063451 . _:b337064610 . _:b337063450 . _:b337063742 . _:b1842458 . _:b337063738 . _:b337064621 . _:b337063461 . _:b337064620 . _:b337063460 . . _:b337064623 . _:b337063463 . _:b337063707 . _:b337064622 . _:b337063462 . _:b337063604 . _:b337064617 . _:b337063457 . _:b337064616 . _:b1842481 . _:b337063456 . _:b337064619 . . _:b337063459 . _:b337064618 . . _:b337064405 . _:b337063458 . _:b337064629 . _:b337064049 . _:b337064377 . _:b337063469 . . _:b337064628 . . _:b337064137 . _:b337063468 . _:b337064631 . . _:b337063624 . _:b337063471 . _:b337064259 . _:b1842485 . _:b337064243 . _:b337064630 . . _:b337063470 . . _:b337064625 . . . _:b337063465 . . _:b337064624 . _:b337063863 . _:b337063464 . _:b337064506 . _:b337064627 . _:b337064156 . _:b337063467 . _:b337064626 . _:b337063466 . _:b337064637 . _:b337063477 . . _:b337064636 . _:b337063476 . _:b337064639 . _:b337063479 . _:b337063526 . _:b337064638 . _:b337063993 . _:b337063478 . _:b337064633 . . _:b337063473 . _:b337064632 . _:b337063466 . _:b337063472 . _:b337064635 . _:b337063475 . _:b337064634 . . _:b337063474 . . _:b337064645 . . _:b337063485 . . _:b337064644 . _:b337063484 . _:b337064647 . . _:b337063487 . _:b337063341 "34"^^ . _:b337064646 . _:b337063347 "26"^^ . _:b1842471 . _:b337063486 . _:b337063340 "34"^^ . _:b337064641 . _:b337063346 "28"^^ . _:b337063481 . . _:b337063328 "86"^^ . _:b337064640 . _:b337063342 "32"^^ . _:b337064407 . _:b337063480 . _:b337063345 "28"^^ . _:b337064643 . _:b337063343 "31"^^ . _:b337064131 . . _:b337063483 . _:b337063344 "29"^^ . _:b337064642 . _:b337063350 "23"^^ . _:b337063338 "39"^^ . _:b337063482 . _:b337064653 . _:b337063351 "23"^^ . _:b337063493 . _:b337064491 . _:b337063329 "65"^^ . _:b337063337 "42"^^ . _:b337064652 . _:b337063492 . _:b337063348 "25"^^ . _:b337063339 "37"^^ . . _:b337064655 . . _:b337063349 "24"^^ . _:b337063495 . _:b337063336 "44"^^ . _:b337064654 . _:b337063335 "44"^^ . _:b337063494 . _:b337063331 "60"^^ . _:b337064649 . _:b337063489 . _:b337063330 "61"^^ . _:b337063352 "22"^^ . _:b337064648 . _:b337063488 . _:b337063355 "21"^^ . _:b337063353 "22"^^ . _:b337064651 . _:b337063622 . _:b337064029 . _:b337063491 . _:b337063354 "21"^^ . _:b337064650 . _:b337063357 "20"^^ . _:b337063490 . _:b337063333 "53"^^ . _:b1842450 . _:b337063356 "20"^^ . _:b337063501 . . _:b337063332 "56"^^ . _:b337063500 . _:b337063359 "20"^^ . _:b337063334 "51"^^ . _:b337063358 "20"^^ . _:b337064424 . _:b337063503 . _:b337063361 "20"^^ . _:b337063502 . _:b337064657 . . _:b337064485 . _:b337063360 "20"^^ . _:b337063497 . _:b337064656 . _:b337063363 "19"^^ . . _:b337063496 . _:b337063362 "19"^^ . _:b337063499 . _:b337064658 . _:b337063365 "19"^^ . . _:b337063498 . _:b337064115 . _:b337063364 "19"^^ . _:b337063509 . _:b337063367 "18"^^ .