STIM1 Gates TRPC Channels, but Not Orai1, by Electrostatic Interaction

Weizhong Zeng, Joseph P. Yuan, Min Seuk Kim, Young Jin Choi, Guo N. Huang, Paul F. Worley, Shmuel Muallem

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Abstract

The receptor-evoked Ca2+ signal includes activation of the store-operated channels (SOCs) TRPCs and the Orais. Although both are gated by STIM1, it is not known how STIM1 gates the channels and whether STIM1 gates the TRPCs and Orais by the same mechanism. Here, we report the molecular mechanism by which STIM1 gates TRPC1, which involves interaction between two conserved, negatively charged aspartates in TRPC1(639DD640) with the positively charged STIM1(684KK685) in STIM1 polybasic domain. Charge swapping and functional analysis revealed that exact orientation of the charges on TRPC1 and STIM1 are required, but all positive-negative charge combinations on TRPC1 and STIM1, except STIM1(684EE685)+TRPC1(639RR640), are functional as long as they are reciprocal, indicating that STIM1 gates TRPC1 by intermolecular electrostatic interaction. Similar gating was observed with TRPC3(697DD698). STIM1 gates Orai1 by a different mechanism since the polybasic and S/P domains of STIM1 are not required for activation of Orai1 by STIM1.

Original languageEnglish
Pages (from-to)439-448
Number of pages10
JournalMolecular Cell
Volume32
Issue number3
DOIs
StatePublished - 7 Nov 2008

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Static Electricity
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Keywords

  • MOLNEURO
  • SIGNALING

Cite this

Zeng, W., Yuan, J. P., Kim, M. S., Choi, Y. J., Huang, G. N., Worley, P. F., & Muallem, S. (2008). STIM1 Gates TRPC Channels, but Not Orai1, by Electrostatic Interaction. Molecular Cell, 32(3), 439-448. https://doi.org/10.1016/j.molcel.2008.09.020
Zeng, Weizhong ; Yuan, Joseph P. ; Kim, Min Seuk ; Choi, Young Jin ; Huang, Guo N. ; Worley, Paul F. ; Muallem, Shmuel. / STIM1 Gates TRPC Channels, but Not Orai1, by Electrostatic Interaction. In: Molecular Cell. 2008 ; Vol. 32, No. 3. pp. 439-448.
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Zeng, W, Yuan, JP, Kim, MS, Choi, YJ, Huang, GN, Worley, PF & Muallem, S 2008, 'STIM1 Gates TRPC Channels, but Not Orai1, by Electrostatic Interaction', Molecular Cell, vol. 32, no. 3, pp. 439-448. https://doi.org/10.1016/j.molcel.2008.09.020

STIM1 Gates TRPC Channels, but Not Orai1, by Electrostatic Interaction. / Zeng, Weizhong; Yuan, Joseph P.; Kim, Min Seuk; Choi, Young Jin; Huang, Guo N.; Worley, Paul F.; Muallem, Shmuel.

In: Molecular Cell, Vol. 32, No. 3, 07.11.2008, p. 439-448.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Zeng, Weizhong

AU - Yuan, Joseph P.

AU - Kim, Min Seuk

AU - Choi, Young Jin

AU - Huang, Guo N.

AU - Worley, Paul F.

AU - Muallem, Shmuel

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AB - The receptor-evoked Ca2+ signal includes activation of the store-operated channels (SOCs) TRPCs and the Orais. Although both are gated by STIM1, it is not known how STIM1 gates the channels and whether STIM1 gates the TRPCs and Orais by the same mechanism. Here, we report the molecular mechanism by which STIM1 gates TRPC1, which involves interaction between two conserved, negatively charged aspartates in TRPC1(639DD640) with the positively charged STIM1(684KK685) in STIM1 polybasic domain. Charge swapping and functional analysis revealed that exact orientation of the charges on TRPC1 and STIM1 are required, but all positive-negative charge combinations on TRPC1 and STIM1, except STIM1(684EE685)+TRPC1(639RR640), are functional as long as they are reciprocal, indicating that STIM1 gates TRPC1 by intermolecular electrostatic interaction. Similar gating was observed with TRPC3(697DD698). STIM1 gates Orai1 by a different mechanism since the polybasic and S/P domains of STIM1 are not required for activation of Orai1 by STIM1.

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