Dissecting ICRAC, a store-operated calcium current

The use of Ca2+ for intracellular signalling necessitates tight local and global control of cytoplasmic Ca2+ concentration, and mechanisms for maintaining the net Ca2+ balance. It has long been recognized that intracellular Ca2+ stores exert control over Ca2+ influx at the plasma membrane through a process of store-operated Ca2+ entry (SOCE). The Ca2+ current ICRAC is the best characterized instance of SOCE, but the elements of the pathway leading to ICRAC have eluded biochemical definition for more than a decade. However, the recent identification of key proteins underlying ICRAC – STIM1 and Orai1 – has led to several insights into this ER-to-plasma membrane signalling system and to the recognition that it is an ancient and conserved mechanism in multicellular organisms.