TRPC channels as STIM1-regulated SOCs

Joseph P. Yuan, Seuk Kim Min, Weizhong Zeng, Min Shin Dong, Guo Huang, Paul F. Worley, Shmuel Muallem

Research output: Contribution to journalArticlepeer-review

86 Citations (Scopus)


Store-operated Ca2+ channels (SOCs) are Ca2+ influx channels at the plasma membrane whose opening is determined by the level of Ca2+ stored in the endoplasmic reticulum lumen. SOCs are activated in response to receptor-mediated or passive depletion of ER Ca2+ to regulate many Ca2+-dependent cellular functions. Early work implicated the TRPC channels as SOCs. More recently, it was found that the Orai channels mediate the CRAC current and that the Ca2+ binding protein STIM1 functions as the ER Ca2+ sensor that mediates activation of the SOCs in response to depletion of ER Ca2+. Key questions are whether both TRPC and Orai channels are opened by STIM1 and the molecular mechanism by which STIM1 opens the SOCs. Ample biochemical and functional evidence indicate interaction of the TRPC channels with STIM1. Furthermore, it was found that STIM1 gates TRPC channels by electrostatic interaction of STIM1(K684,K685) in the polybasic domain of STIM1 with two negative charges (aspartates or glutamates) that are conserved in all TRPC channels. Charge mutants of STIM1(K684,K685) and TRPC1(D639,D640) and TRPC3(D697D698) were used to develop further direct evidence for the function of TRPC channels as SOCs. The evidence in favor of TRPC channels as SOCs are discussed.

Original languageEnglish
Pages (from-to)221-225
Number of pages5
Issue number4
Publication statusPublished - 2009

Bibliographical note

Funding Information:
This work was supported by the National Natural Science Foundation of China ( 51551201 and 51772137 ) and the Fundamental Research Funds for the Central Universities (lzujbky-2019-sp03).

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry


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