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The CRAC channel activator STIM1 binds and inhibits L-type voltage-gated calcium channels

Chan Young Park1, Aleksandr Shcheglovitov, Ricardo Dolmetsch

  • 1Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Science (New York, N.Y.)
|October 9, 2010
PubMed

Insights

Stromal interaction molecule 1 (STIM1) inhibits voltage-gated calcium channels (CaV1.2), revealing a new regulatory mechanism. This finding explains how cells coordinate different calcium channel activities for coherent signaling.

Area of Science:

  • Cellular Biology
  • Molecular Physiology
  • Ion Channel Function

Background:

  • Voltage-gated calcium channels (CaV) and store-operated calcium channels are key for cellular calcium entry.
  • The coordination between these channels is crucial for generating coherent calcium signals, but the underlying mechanisms are poorly understood.

Purpose of the Study:

  • To investigate the regulatory relationship between STIM1, a store-operated calcium channel activator, and voltage-gated calcium channels.
  • To elucidate the molecular mechanisms governing the reciprocal regulation of these calcium channels.

Main Methods:

  • Investigated the interaction between STIM1 and the voltage-gated calcium channel CaV1.2.
  • Utilized molecular binding assays and electrophysiological techniques to assess channel activity and localization.

Main Results:

  • Stromal interaction molecule 1 (STIM1) directly suppresses the opening of voltage-gated calcium channel CaV1.2.
  • STIM1 binds to the C terminus of CaV1.2, acutely inhibiting its gating and causing long-term channel internalization.
  • Identified a novel function for STIM1 in regulating voltage-gated calcium channels.

Conclusions:

  • STIM1 plays a previously unrecognized role in suppressing voltage-gated calcium channel activity.
  • This study provides a molecular basis for the reciprocal regulation of store-operated and voltage-gated calcium channels.
  • Understanding this interaction is vital for comprehending cellular calcium signaling dynamics.

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