Dissecting ICRAC, a store-operated calcium current.

The use of Ca(2+) for intracellular signalling necessitates tight local and global control of cytoplasmic Ca(2+) concentration, and mechanisms for maintaining the net Ca(2+) balance. It has long been recognized that intracellular Ca(2+) stores exert control over Ca(2+) influx at the plasma membrane through a process of store-operated Ca(2+) entry (SOCE). The Ca(2+) current I(CRAC) is the best characterized instance of SOCE, but the elements of the pathway leading to I(CRAC) have eluded biochemical definition for more than a decade. However, the recent identification of key proteins underlying I(CRAC)--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.