CD95 signaling via ceramide-rich membrane rafts - PubMed (original) (raw)

. 2001 Jun 8;276(23):20589-96.

doi: 10.1074/jbc.M101207200. Epub 2001 Mar 12.

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CD95 signaling via ceramide-rich membrane rafts

H Grassme et al. J Biol Chem. 2001.

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Abstract

Clustering seems to be employed by many receptors for transmembrane signaling. Here, we show that acid sphingomyelinase (ASM)-released ceramide is essential for clustering of CD95. In vitro and in vivo, extracellularly orientated ceramide, released upon CD95-triggered translocation of ASM to the plasma membrane outer surface, enabled clustering of CD95 in sphingolipid-rich membrane rafts and apoptosis induction. Whereas ASM deficiency, destruction of rafts, or neutralization of surface ceramide prevented CD95 clustering and apoptosis, natural ceramide only rescued ASM-deficient cells. The data suggest CD95-mediated clustering by ceramide is prerequisite for signaling and death.

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