FIGURE 6.

Hypothetical scheme of RyR action in T cells. Store depletion causes translocation of STIM1, ORAI1, and RyR to the ER-plasma membrane (PM) junctional sites. STIM1 interacts with ORAI1 to open CRAC channels. Ca²⁺ that entered the cell via CRAC channels activates RyR that are in close proximity to CRAC channel clusters. SERCA pumps the Ca²⁺, which entered the cell via CRAC channels, into the ER lumen. Ca²⁺ leaks from the ER via RyR located in close proximity to STIM1. The local decline in [Ca²⁺]_ER in the vicinity of STIM1 Ca²⁺-sensing domains stabilizes STIM1/ORAI1 coupling, which prevents CRAC channel inactivation in the presence of SOCE and global ER refilling.