CRAC channels in secretory epithelial cell function and disease

The receptor-evoked Ca2+ signal in secretory epithelia mediate many cellular functions essential for cell survival and their most fundamental functions of secretory granules exocytosis and fluid and electrolyte secretion. Ca2+ influx is a key component of the receptor-evoked Ca2+ signal in secretory cell and is mediated by both TRPC and the STIM1-activated Orai1 channels that mediates the Ca2+ release-activated current (CRAC) I-crac. The core components of the receptor-evoked Ca2+ signal are assembled at the ER/PM junctions where exchange of materials between the plasma membrane and internal organelles take place, including transfer of lipids and Ca2+. The Ca2+ signal generated at the confined space of the ER/PM junctions is necessary for activation of the Ca2+-regulated proteins and ion channels that mediate exocytosis with high fidelity and tight control. In this review we discuss the general properties of Ca2+ signaling, PI(4,5)P-2 and other lipids at the ER/PM junctions with regard to secretory cells function and disease caused by uncontrolled Ca2+ influx.