Emerging perspectives in store-operated Ca2+ entry: roles of Orai, Stim and TRP.

Abstract Depletion of intracellular Ca 2+ stores induces Ca 2+ influx across the plasma membrane through store-operated channels (SOCs). This store-operated Ca 2+ influx is important for the replenishment of the Ca 2+ stores, and is also involved in many signaling processes by virtue of the ability of intracellular Ca 2+ to act as a second messenger. For many years, the molecular identities of particular SOCs, as well as the signaling mechanisms by which these channels are activated, have been elusive. Recently, however, the mammalian proteins STIM1 and Orai1 were shown to be necessary for the activation of store-operated Ca 2+ entry in a variety of mammalian cells. Here we present molecular, pharmacological, and electrophysiological properties of SOCs, with particular focus on the roles that STIM1 and Orai1 may play in the signaling processes that regulate various pathways of store-operated entry.