STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels.
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ABSTRACT:
SUBMITTER: Yuan JP
PROVIDER: S-EPMC2699187 | biostudies-literature | 2007 Jun
REPOSITORIES: biostudies-literature
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STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels.
Yuan Joseph P JP Zeng Weizhong W Huang Guo N GN Worley Paul F PF Muallem Shmuel S
Nature cell biology 20070507 6
Stromal interacting molecule 1 (STIM1) is a Ca(2+) sensor that conveys the Ca(2+) 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 La(3+), suggesting that STIM1 is obligatory for activation of TRPC channels by agonists, but STIM1 is not essential for channel function. ...[more]
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Project description:Recent human genetic studies have shown that G?5 is related to various clinical symptoms, such as sinus bradycardia, cognitive disability, and attention deficit hyperactivity disorder. Although the calcium signaling cascade is closely associated with a heterotrimeric G-protein, the function of G?5 in calcium signaling and its relevance to clinical symptoms remain unknown. In this study, we investigated the in vitro changes of store-operated calcium entry (SOCE) with exogenous expression of G?5. The cells expressing G?5 had enhanced SOCE after depletion of calcium ion inside the endoplasmic reticulum. G?5 also augmented Stim1- and Orai1-dependent SOCE. An ORAI1 loss-of-function mutant did not show inhibition of G?5-induced SOCE, and a STIM1-ERM truncation mutant showed no enhancement of SOCE. These results suggested a novel role of GNB5 and Stim1, and provided insight into the regulatory mechanism of SOCE.
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