Figure 2.

SOCE and Ca²⁺ Tunneling. SOCE is activated in response to a decrease in Ca²⁺ levels in the ER following Ca²⁺ release. This leads to a conformational change in STIM1 and its translocation to ER-PM junctions where it recruits and gates Orai1 allowing Ca²⁺ influx into the SOCE microdomain. During Ca²⁺ signaling in response to agonist with open IP₃ receptors, Ca²⁺ flowing through Orai1 is taken up by SERCA at ER-PM junctions and diffuses to open IP₃ receptors that are distant from the SOCE microdomain thus allowing Ca²⁺ release to activate distal effectors.