Store-Operated Calcium Channels: New Perspectives on Mechanism and Function

Store-operated calcium channels (SOCs) are a nearly ubiquitous Ca2+ entry pathway stimulated by numerous cell surface receptors via the reduction of Ca2+ concentration in the ER. The discovery of STIM proteins as ER Ca2+ sensors and Orai proteins as structural components of the Ca2+ release-activated Ca2+ (CRAC) channel, a prototypic SOC, opened the floodgates for exploring the molecular mechanism of this pathway and its functions. This review focuses on recent advances made possible by the use of STIM and Orai as molecular tools. I will describe our current understanding of the store-operated Ca2+ entry mechanism and its emerging roles in physiology and disease, areas of uncertainty in which further progress is needed, and recent findings that are opening new directions for research in this rapidly growing field.