New insights into the activation mechanism of store-operated calcium channels: roles of STIM and Orai

The activation of Ca2 entry through store-operated channels by agonists that deplete Ca2 from the endoplasmic reticulum (ER)is a ubiquitous signaling mechanism,the molecular basis of which has remained elusive for the past two decades.Store-operated Ca2 -release-activated Ca2 (CRAC)channels constitute the sole pathway for Ca2 entry following antigen-receptor engagement.In a set of breakthrough studies over the past two years,stromal interaction molecule l(STIM1,tbe ER Ca2 sensor) and Orail(a pore-forming subunit of the CRAC channel)have been identified.Here we review these recent studies and the insights they provide into the mechanism of store-operated Ca2 channels(SOCCs).