Figure 8

Schematic illustration of calcium signaling in non-excitable cells. Following the stimulation of G protein-coupled receptors (GPCR), phospholipase C (PLC) hydrolyses PIP2 to IP3. IP3 activates the IP3 receptor (IP3R) and triggers the depletion of ER Ca²⁺ stores. TG or ionomycin also cause the Ca²⁺ depletion from ER by different mechanisms. Declined ER Ca²⁺ levels are sensed by STIM1 proteins. STIM1 oligomerizes, migrates towards subplasmalemmal ER-PM junctions, and interacts with Orai1 to trigger store-operated calcium channel opening. Then, SERCA pumps Ca²⁺ back into the ER to refill the stores with Ca²⁺. SLC10A7 is hypothesized to negatively regulate STIM1, Orai1 and/or SERCA2 through protein interaction. TG, SERCA inhibitor; BTP-2, SOCE blocker.