Editors' ChoiceCalcium signaling

Channel STIMulation

Sci. Signal.  05 Oct 2010:
Vol. 3, Issue 142, pp. ec308
DOI: 10.1126/scisignal.3142ec308

The STIM1 protein functions as a calcium sensor and regulates entry of calcium into cells across the plasma membrane. When cell surface receptors are stimulated and cause release of calcium from internal stores in the endoplasmic reticulum (ER), STIM proteins in the ER membrane interact with the Orai channel pore protein in the plasma membrane to allow calcium entry from the outside of the cell (see the Perspective by Cahalan). Park et al. and Wang et al. now show that STIM also acts to suppress conductance by another calcium channel—the voltage-operated CaV1.2 channel. STIM1 appeared to interact directly with CaV1.2 channels in multiple cell types, including vascular smooth muscle cells, neurons, and cultured cells derived from T lymphocytes. The interaction inhibited opening of the CaV1.2 channels and caused depletion of the channel from the cell surface.

C. Y. Park, A. Shcheglovitov, R. Dolmetsch, The CRAC channel activator STIM1 binds and inhibits L-type voltage-gated calcium channels. Science 330, 101–105 (2010). [Abstract] [Full Text]

Y. Wang, X. Deng, S. Mancarella, E. Hendron, S. Eguchi, J. Soboloff, X. D. Tang, D. L. Gill, The calcium store sensor, STIM1, reciprocally controls Orai and CaV1.2 channels. Science 330, 105–109 (2010). [Abstract] [Full Text]

M. D. Cahalan, How to STIMulate calcium channels. Science 330, 43–44 (2010). [Abstract] [Full Text]