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STIM1 gates TRPC channels, but not Orai1, by electrostatic interaction

Weizhong Zeng1, Joseph P Yuan, Min Seuk Kim

  • 1Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Molecular Cell
|November 11, 2008
PubMed

Insights

Stromal interaction molecule 1 (STIM1) gates TRPC1 channels via electrostatic interactions between charged amino acids. This mechanism differs from how STIM1 gates Orai1 channels.

Area of Science:

  • Cellular biology
  • Molecular mechanisms of ion channel gating

Background:

  • Receptor-evoked calcium signals involve store-operated channels (SOCs) like TRPC and Orai channels.
  • STIM1 is known to gate both TRPC and Orai channels, but the precise gating mechanisms remain unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism by which STIM1 gates the TRPC1 channel.
  • To determine if STIM1 employs the same gating mechanism for TRPC and Orai channels.

Main Methods:

  • Investigated the interaction between STIM1 and TRPC1 using charge-swapping mutations.
  • Performed functional analysis of mutated STIM1 and TRPC1 proteins.
  • Compared STIM1 gating mechanisms for TRPC1 and Orai1.

Main Results:

  • STIM1 gates TRPC1 through intermolecular electrostatic interactions between conserved charged residues (STIM1 KK684-685 and TRPC1 DD639-640).
  • Specific charge orientation is crucial, but reciprocal charge combinations enable functional gating.
  • STIM1 also gates TRPC3 via a similar electrostatic mechanism.
  • STIM1 gates Orai1 through a distinct mechanism not requiring STIM1's polybasic and S/P domains.

Conclusions:

  • STIM1 utilizes an electrostatic interaction mechanism to gate TRPC1 and TRPC3 channels.
  • The gating mechanism for Orai1 by STIM1 is different from that of TRPC channels.
  • This study reveals distinct molecular strategies employed by STIM1 for gating different SOC families.

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