STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels

Joseph P. Yuan, Weizhong Zeng, Guo N. Huang, Paul F. Worley, Shmuel Muallem

Research output: Contribution to journalArticleResearchpeer-review

364 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)636-645
Number of pages10
JournalNature Cell Biology
Volume9
Issue number6
DOIs
StatePublished - 1 Jun 2007

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Endoplasmic Reticulum
Cluster Analysis
Cell Membrane

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Yuan, Joseph P. ; Zeng, Weizhong ; Huang, Guo N. ; Worley, Paul F. ; Muallem, Shmuel. / STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels. In: Nature Cell Biology. 2007 ; Vol. 9, No. 6. pp. 636-645.
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STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels. / Yuan, Joseph P.; Zeng, Weizhong; Huang, Guo N.; Worley, Paul F.; Muallem, Shmuel.

In: Nature Cell Biology, Vol. 9, No. 6, 01.06.2007, p. 636-645.

Research output: Contribution to journalArticleResearchpeer-review

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