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

Abstract

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.