TRPC channels as STIM1-regulated store-operated channels

Paul F. Worley, Weizhong Zeng, Guo N. Huang, Joseph P. Yuan, Joo Young Kim, Min Goo Lee, Shmuel Muallem

Research output: Contribution to journalArticleResearchpeer-review

161 Citations (Scopus)

Abstract

Receptor-activated Ca2+ influx is mediated largely by store-operated channels (SOCs). TRPC channels mediate a significant portion of the receptor-activated Ca2+ influx. However, whether any of the TRPC channels function as a SOC remains controversial. Our understanding of the regulation of TRPC channels and their function as SOCs is being reshaped with the discovery of the role of STIM1 in the regulation of Ca2+ influx channels. The findings that STIM1 is an ER resident Ca2+ binding protein that regulates SOCs allow an expanded and molecular definition of SOCs. SOCs can be considered as channels that are regulated by STIM1 and require the clustering of STIM1 in response to depletion of the ER Ca2+ stores and its translocation towards the plasma membrane. TRPC1 and other TRPC channels fulfill these criteria. STIM1 binds to TRPC1, TRPC2, TRPC4 and TRPC5 but not to TRPC3, TRPC6 and TRPC7, and STIM1 regulates TRPC1 channel activity. Structure-function analysis reveals that the C-terminus of STIM1 contains the binding and gating function of STIM1. The ERM domain of STIM1 binds to TRPC channels and a lysine-rich region participates in the gating of SOCs and TRPC1. Knock-down of STIM1 by siRNA and prevention of its translocation to the plasma membrane inhibit the activity of native SOCs and TRPC1. These findings support the conclusion that TRPC1 is a SOC. Similar studies with other TRPC channels demonstrate their regulation by STIM1 and indicate that all TRPC channels, except TRPC7, function as SOCs.

Original languageEnglish
Pages (from-to)205-211
Number of pages7
JournalCell Calcium
Volume42
Issue number2
DOIs
StatePublished - 1 Jan 2007

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Cell Membrane
Small Interfering RNA
Lysine
Cluster Analysis
Carrier Proteins

Keywords

  • SOCs
  • STIM1
  • TRPC channels

Cite this

Worley, P. F., Zeng, W., Huang, G. N., Yuan, J. P., Kim, J. Y., Lee, M. G., & Muallem, S. (2007). TRPC channels as STIM1-regulated store-operated channels. Cell Calcium, 42(2), 205-211. https://doi.org/10.1016/j.ceca.2007.03.004
Worley, Paul F. ; Zeng, Weizhong ; Huang, Guo N. ; Yuan, Joseph P. ; Kim, Joo Young ; Lee, Min Goo ; Muallem, Shmuel. / TRPC channels as STIM1-regulated store-operated channels. In: Cell Calcium. 2007 ; Vol. 42, No. 2. pp. 205-211.
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Worley, PF, Zeng, W, Huang, GN, Yuan, JP, Kim, JY, Lee, MG & Muallem, S 2007, 'TRPC channels as STIM1-regulated store-operated channels', Cell Calcium, vol. 42, no. 2, pp. 205-211. https://doi.org/10.1016/j.ceca.2007.03.004

TRPC channels as STIM1-regulated store-operated channels. / Worley, Paul F.; Zeng, Weizhong; Huang, Guo N.; Yuan, Joseph P.; Kim, Joo Young; Lee, Min Goo; Muallem, Shmuel.

In: Cell Calcium, Vol. 42, No. 2, 01.01.2007, p. 205-211.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - TRPC channels as STIM1-regulated store-operated channels

AU - Worley, Paul F.

AU - Zeng, Weizhong

AU - Huang, Guo N.

AU - Yuan, Joseph P.

AU - Kim, Joo Young

AU - Lee, Min Goo

AU - Muallem, Shmuel

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AB - Receptor-activated Ca2+ influx is mediated largely by store-operated channels (SOCs). TRPC channels mediate a significant portion of the receptor-activated Ca2+ influx. However, whether any of the TRPC channels function as a SOC remains controversial. Our understanding of the regulation of TRPC channels and their function as SOCs is being reshaped with the discovery of the role of STIM1 in the regulation of Ca2+ influx channels. The findings that STIM1 is an ER resident Ca2+ binding protein that regulates SOCs allow an expanded and molecular definition of SOCs. SOCs can be considered as channels that are regulated by STIM1 and require the clustering of STIM1 in response to depletion of the ER Ca2+ stores and its translocation towards the plasma membrane. TRPC1 and other TRPC channels fulfill these criteria. STIM1 binds to TRPC1, TRPC2, TRPC4 and TRPC5 but not to TRPC3, TRPC6 and TRPC7, and STIM1 regulates TRPC1 channel activity. Structure-function analysis reveals that the C-terminus of STIM1 contains the binding and gating function of STIM1. The ERM domain of STIM1 binds to TRPC channels and a lysine-rich region participates in the gating of SOCs and TRPC1. Knock-down of STIM1 by siRNA and prevention of its translocation to the plasma membrane inhibit the activity of native SOCs and TRPC1. These findings support the conclusion that TRPC1 is a SOC. Similar studies with other TRPC channels demonstrate their regulation by STIM1 and indicate that all TRPC channels, except TRPC7, function as SOCs.

KW - SOCs

KW - STIM1

KW - TRPC channels

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Worley PF, Zeng W, Huang GN, Yuan JP, Kim JY, Lee MG et al. TRPC channels as STIM1-regulated store-operated channels. Cell Calcium. 2007 Jan 1;42(2):205-211. https://doi.org/10.1016/j.ceca.2007.03.004