Unlocking SOAR releases STIM

Abstract

A crucial component of the receptor-evoked Ca2+ signal is Ca2+ influx mediated by the store-operated Ca2+ channels (SOCs). The molecular makeup of one SOC is the endoplasmic reticulum (ER) Ca2+ sensor STIM1 and the pore-forming Orai1. Ca2+ release from the ER leads to co-clustering of STIM1 and Orai1 to activate Orai1. The short STIM1 SOAR/CAD domain (STIM1 Orai1-activating region/CRAC-activating domain), which has two coiledcoil (C-C) domains, interacts with the Orai1 C terminus C-C domain to activate the channel. How the function of SOAR is regulated is not known. Korzeniowski et al (2010) and Muik et al (2011; this issue) now identified an autoinhibitory domain in STIM1 that occludes SOAR. Release of SOAR involves a conformational transition that is aided by the Orai1 C-C domain. © 2011 European Molecular Biology Organization.