IP3 receptors and store-operated Ca2+ entry: a license to fill

Abstract

Inositol 1,4,5-trisphosphate receptors (IP₃Rs) are widely expressed intracellular Ca²⁺ channels that evoke large local increases in cytosolic Ca²⁺ concentration. By depleting the ER of Ca²⁺, IP₃Rs also activate store-operated Ca²⁺ entry (SOCE). Immobile IP₃Rs close to the plasma membrane (PM) are the only IP₃Rs that respond to physiological stimuli. The association of these 'licensed' IP₃Rs with the ER-PM junctions where STIM interacts with Orai PM Ca²⁺ channels may define the autonomous functional unit for SOCE. Ca²⁺ entering cells through SOCE can be delivered directly to specific effectors, or it may reach them only after the Ca²⁺ has been sequestered by the ER and then released through IP₃Rs. This 'tunnelling' of Ca²⁺ through the ER to IP₃Rs selectively delivers Ca²⁺ to different effectors.