Fig. 4.

Orai1-driven Ca²⁺ entry delays the irreversible induction of the CD95-mediated apoptotic signal. (A) Kinetics of death induction measured by mitochondrial potential, delayed by overexpression of Orai1 and accelerated by expression of Orai1E106A. The indicated cells were incubated for 6 h with 10 ng/mL of CD95L, a concentration that triggers 100% cell death in Jurkat-GFP cells. Blocking anti-CD95 mAb ZB4 or isotype control mAb (2.5 μg/mL) was added at the indicated times. Cell death was assessed after 6 h by measuring the decrease in ΔΨm. The percentage of “rescued cells” was estimated as follows: [100 − (dead cells with blocking anti-CD95 mAb/dead cells with isotype control mAb) × 100]. (B) Schematic summary of the CD95-mediated Ca²⁺ response. CD95 engagement elicits the PLCγ1 activation, which in turn mobilizes the ER-stored Ca²⁺ through IP₃ receptor activation, leading to STIM1/Orai1-driven entry of Ca²⁺. The localized Ca²⁺ entry redistributes PKCβ2 to the CD95-Cap, where the kinase activity hinders DISC formation.