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

Science. 2010 Oct 1;330(6000):101-5. doi: 10.1126/science.1191027.

Abstract

Voltage- and store-operated calcium (Ca(2+)) channels are the major routes of Ca(2+) entry in mammalian cells, but little is known about how cells coordinate the activity of these channels to generate coherent calcium signals. We found that STIM1 (stromal interaction molecule 1), the main activator of store-operated Ca(2+) channels, directly suppresses depolarization-induced opening of the voltage-gated Ca(2+) channel Ca(V)1.2. STIM1 binds to the C terminus of Ca(V)1.2 through its Ca(2+) release-activated Ca(2+) activation domain, acutely inhibits gating, and causes long-term internalization of the channel from the membrane. This establishes a previously unknown function for STIM1 and provides a molecular mechanism to explain the reciprocal regulation of these two channels in cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels, L-Type / chemistry
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / metabolism*
  • Calcium Signaling
  • Cell Line
  • Cell Membrane / metabolism*
  • Humans
  • Ion Channel Gating
  • Jurkat Cells
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Models, Biological
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Protein Binding
  • Protein Structure, Tertiary
  • Rats
  • Rats, Sprague-Dawley
  • Stromal Interaction Molecule 1
  • T-Lymphocytes / metabolism*

Substances

  • Calcium Channels, L-Type
  • L-type calcium channel alpha(1C)
  • Membrane Proteins
  • Neoplasm Proteins
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • Calcium