Abstract
Recent genome-wide RNAi screens have revealed Stim and Orai as critical components of the Ca2+ release-activated Ca2+ (CRAC) channel. Upon release of Ca2+ from the ER, Stim senses Ca2+depletion, aggregates, relocalizes to ER-plasma membrane (PM) junctions, and interacts with Orai pore-forming subunits in the PM to open the CRAC channel. This signaling cascade is spatially confined, regulated by specific protein-protein interactions between Stim and Orai, and may require additional binding proteins such as regulatory subunits, trafficking proteins, or kinases.
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