Fig 7. Schematic diagram illustrating the role of TRIC-A in limiting SOCE and oscillatory Ca²⁺ signals by interfering with STIM1/Orai1 complex assembly.

Left: Upon ER Ca²⁺ depletion via RyR/IP₃R, STIM1 loses bound Ca²⁺ from its EF-hand, undergoes a conformational change, oligomerizes, and translocates into clusters at ER–PM junctions. STIM1 then recruits Orai1 channels into the clusters and activates the Ca²⁺-selective pore for subsequent Ca²⁺ entry into the cells to sustain RyR/IP₃R-triggered Ca²⁺ oscillations. Right: TRIC-A translocates along with STIM1 to ER–PM junctions, where it interferes with STIM1/Orai1 coupling, which consequently limits the Ca²⁺ influx via Orai1 (SOCE) and the frequency of cytosolic Ca²⁺ oscillations. ER, endoplasmic reticulum; I_CRAC, Ca²⁺ release-activated Ca²⁺ current; IP₃R, inositol 1,4,5-triphosphate receptor; Orai1, Ca²⁺-release–activated Ca²⁺ channel 1; PM, plasma membrane; RyR, ryanodine receptor; SOCE, store-operated Ca²⁺ entry; STIM1, stromal interaction molecule 1; TRIC, trimeric intracellular cation.