Store-operated CRAC channels

In many animal cells, store-operated Ca2⁺ release-activated Ca2⁺ (CRAC) channels function as an essential route for Ca2⁺ entry. CRAC channels control fundamental cellular functions including gene expression, motility, and cell proliferation and are involved in the etiology of several disease processes including a severe combined immunodeciency syndrome. With several distinguishing biophysical and molecular features, CRAC channels are constructed as a two-component system consisting of the stromal interaction molecule (STIM) proteins, which serve as the ER Ca2⁺ sensors, and the ORAI proteins, which form the channel pores. ER Ca2⁺ store depletion evokes direct interactions between the STIM sensors and the ORAI channels, driving their redistribution and accumulation into overlapping puncta at peripheral cellular sites to elicit localized elevations of [Ca2⁺]i at clusters of CRAC channels. is chapter examines the molecular features of the STIM and ORAI proteins that regulate the operation of CRAC channels and highlights their physiological roles in select organ systems.