Ca²⁺ influx at the ER/PM junctions

Ca²⁺ influx across the plasma membrane is a key component of the receptor-evoked Ca²⁺ signaling that mediate numerous cell functions and reload the ER after partial or full ER Ca²⁺ store depletion. Ca²⁺ influx is activated in response to Ca²⁺ release from the ER, a concept developed by Jim Putney, and the channels mediating the influx are thus called store-operated Ca²⁺ influx channels, or SOCs. The molecular identity of the SOCs has been determined with the identification of the TRPC channels, STIM1 and the Orai channels. These channels are targeted to, operate and are regulated when at the ER/PM junctions. ER/PM junctions are a form of membrane contact sites (MCSs) that are present in all parts of the cells, where the ER makes contacts with cellular membranes and organelles. MCSs have many cellular functions, and are the sites of lipid and Ca²⁺ transport and delivery between organelles. This short review discusses aspects of MCSs in the context of Ca²⁺ transport.