The CRAC Channel Activator STIM1 Binds and Inhibits L-Type Voltage-Gated Calcium Channels

Channel STIMulation 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. (p. 101 ) and Wang et al. (p. 105 ) now show that STIM also acts to suppress conductance by another calcium channel—the voltage-operated Ca V 1.2 channel. STIM1 appeared to interact directly with Ca V 1.2 channels in multiple cell types, including vascular smooth muscle cells, neurons, and cultured cells derived from T lymphocytes. The interaction inhibited opening of the Ca V 1.2 channels and caused depletion of the channel from the cell surface.