期刊
NATURE CELL BIOLOGY
卷 9, 期 6, 页码 636-U38出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb1590
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- NIDA NIH HHS [R01 DA010309-08, DA00266, R01 DA010309, R01 DA010309-07, P50 DA000266-310015, R37 DA010309, R01 DA010309-09, P50 DA000266-370017, R01 DA010309-06, R01 DA010309-04, P50 DA000266-360017, P50 DA000266, DA10309, R01 DA010309-05] Funding Source: Medline
- NIDCR NIH HHS [R01 DE012309-10, R01 DE012309-03, R01 DE012309-11, DE12309, R01 DE012309-05, R01 DE012309-08, R01 DE012309-06, R01 DE012309-07, R01 DE012309-12, R01 DE012309-09, R01 DE012309, R01 DE012309-04] Funding Source: Medline
- NIDDK NIH HHS [R01 DK038938-17, R01 DK038938-23, R01 DK038938-18, R01 DK038938-24, R01 DK038938-21, R01 DK038938, DK38938, R01 DK038938-16, R01 DK038938-15, R01 DK038938-14, R01 DK038938-19, R01 DK038938-22, R01 DK038938-20] Funding Source: Medline
- NIMH NIH HHS [P50 MH068830-010002, P50 MH068830-040002, P50 MH068830-030002, P50 MH068830-050002, P50 MH068830, MH068830, P50 MH068830-020002] Funding Source: Medline
- NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [R01DE012309] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK038938] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [P50MH068830] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [R37DA010309, R01DA010309, P50DA000266] Funding Source: NIH RePORTER
Stromal interacting molecule 1 (STIM1) is a Ca2+ sensor that conveys the Ca2+ load of the endoplasmic reticulum to store-operated channels (SOCs) at the plasma membrane. Here, we report that STIM1 binds TRPC1, TRPC4 and TRPC5 and determines their function as SOCs. Inhibition of STIM1 function inhibits activation of TRPC5 by receptor stimulation, but not by La3+, suggesting that STIM1 is obligatory for activation of TRPC channels by agonists, but STIM1 is not essential for channel function. Through a distinct mechanism, STIM1 also regulates TRPC3 and TRPC6. STIM1 does not bind TRPC3 and TRPC6, and regulates their function indirectly by mediating the heteromultimerization of TRPC3 with TRPC1 and TRPC6 with TRPC4. TRPC7 is not regulated by STIM1. We propose a new definition of SOCs, as channels that are regulated by STIM1 and require the store depletion-mediated clustering of STIM1. By this definition, all TRPC channels, except TRPC7, function as SOCs.
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