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

Depletion of intracellular Ca²⁺ stores induces Ca²⁺ influx across the plasma membrane through store-operated channels (SOCs). This store-operated Ca²⁺ influx is important for the replenishment of the Ca²⁺ stores, and is also involved in many signaling processes by virtue of the ability of intracellular Ca²⁺ 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 Ca²⁺ 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.