Figure 9. Model summarizing altered functions of STIM1A.

Left image: SOCE mediated by STIM1 and ORAI1 leads to Ca²⁺ influx, and recruitment of the AKAP79/NFAT signaling complex and the phosphodiesterase PDE8. Locally recruited PDE8 reduces cAMP at ER‐PM junctions. The AKAP79 signalosome recruitment is instable due to limited membrane PIP2 levels. CAN: calcineurin. Right image: SOCE mediated by STIM1A and ORAI1 leads to reduced Ca²⁺ influx due to destabilized gating and hampers recruitment of PDE8. Reduced recruitment leads to reduced local cAMP degradation, which enhances PIP₂ levels by activating PIP kinases. Increased levels of PIP₂ stabilize the AKAP79 signalosome, enabling more efficient NFAT translocation.