Hypothetical model for CD47-induced PS exposure.

Two nonmutually exclusive pathways leading to PS exposure and initiated by a common triggering event: Cdc42/WASP signaling pathway and F-actin polymerization. Inhibition by cytochalasin D (Ctyo D). Pathway no. 1 (thin arrow): loss in ΔΨm followed by PS externalization. Antimycin A inhibits PS but not ΔΨm loss. Pathway no. 2 (thick arrow): bypass of mitochondria and direct induction of PS externalization. Elevated extracellular K⁺ slows down PS exposure. Absence of caspase activation and nuclear degradation in CD47-induced cell death. Dotted arrows indicate hypothetical inhibitory pathways. ROS indicates reactive oxygen species; AIF, apoptosis-inducing factor; Cyt c, cytochrome c.