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 journalArticleResearchpeer-review

85 Citations (Scopus)

Abstract

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
JournalChannels
Volume3
Issue number4
DOIs
StatePublished - 1 Jan 2009

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Glutamates
Static Electricity
Aspartic Acid
Endoplasmic Reticulum
Carrier Proteins
Cell Membrane
Cell membranes
Coulomb interactions
Chemical activation
Sensors
Calcium Release Activated Calcium Channels

Keywords

  • Electrostatic interaction
  • Gating
  • SOCs
  • STIM1
  • TRPC channels

Cite this

Yuan, J. P., Min, S. K., Zeng, W., Dong, M. S., Huang, G., Worley, P. F., & Muallem, S. (2009). TRPC channels as STIM1-regulated SOCs. Channels, 3(4). https://doi.org/10.4161/chan.3.4.9198
Yuan, Joseph P. ; Min, Seuk Kim ; Zeng, Weizhong ; Dong, Min Shin ; Huang, Guo ; Worley, Paul F. ; Muallem, Shmuel. / TRPC channels as STIM1-regulated SOCs. In: Channels. 2009 ; Vol. 3, No. 4.
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Yuan, JP, Min, SK, Zeng, W, Dong, MS, Huang, G, Worley, PF & Muallem, S 2009, 'TRPC channels as STIM1-regulated SOCs', Channels, vol. 3, no. 4. https://doi.org/10.4161/chan.3.4.9198

TRPC channels as STIM1-regulated SOCs. / Yuan, Joseph P.; Min, Seuk Kim; Zeng, Weizhong; Dong, Min Shin; Huang, Guo; Worley, Paul F.; Muallem, Shmuel.

In: Channels, Vol. 3, No. 4, 01.01.2009.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - TRPC channels as STIM1-regulated SOCs

AU - Yuan, Joseph P.

AU - Min, Seuk Kim

AU - Zeng, Weizhong

AU - Dong, Min Shin

AU - Huang, Guo

AU - Worley, Paul F.

AU - Muallem, Shmuel

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Y1 - 2009/1/1

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AB - 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.

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DO - 10.4161/chan.3.4.9198

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JO - Channels

JF - Channels

SN - 1933-6950

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ER -

Yuan JP, Min SK, Zeng W, Dong MS, Huang G, Worley PF et al. TRPC channels as STIM1-regulated SOCs. Channels. 2009 Jan 1;3(4). https://doi.org/10.4161/chan.3.4.9198