A model for Fas-induced capping through ASMase activation. Ligation of preformed Fas trimers on a target cell by transmembrane Fas ligand (FasL) activates small amounts of caspase-8 within the cytoplasm of that cell, which is nonetheless sufficient to induce ASMase translocation into membrane rafts. The consequent hydrolysis of SM to ceramide, which self-associates, initiates coalescence of ceramide-enriched rafts into larger patches (isolated ovals) and platforms (aggregated ovals). Only ligated Fas can enter and concentrate within these platforms, permitting oligomerization of the downstream Fas effectors FADD and caspase-8 (not shown), the constituents of the death-inducing signaling complex (DISC). The extent to which this raft reorganization system is used for Fas signaling is currently unknown. Fas may not be the only cell surface receptor to employ this concentrating system, as a recent study suggests that CD40 may also cap in ceramide-rich platforms (61). Note that the transmembrane domains of some, and the cytoplasmic domain of all, Fas molecules are not depicted in this schematic for reasons of clarity. Similarly, the FasL-presenting cell is only shown once (upper left). PM, plasma membrane.