Molecular mechanisms of ceramide-mediated CD95 clustering

Receptor clustering has been suggested as a crucial mechanism to initiate r eceptor signaling Here we show that ceramide in sphingolipid-rich membrane rafts mediates clustering of CD95. Neutralization of surface ceramide or in hibition of its endogenous generation prevented CD95 clustering. Furthermor e, application of ceramide at the cell surface triggered clustering of acti ve but not inactive CD95. Apoptosis was inhibited by neutralization of surf ace ceramide or inhibition of ceramide release in vitro and in vivo. Thus, we conclude that surface ceramide mediates CD95 clustering, which is requir ed for initiation of apoptosis, at least in some cell types. (C) zool Acade mic Press.