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CD95 signaling via ceramide-rich membrane rafts.

The Journal of biological chemistry (2001-03-30)
H Grassme, A Jekle, A Riehle, H Schwarz, J Berger, K Sandhoff, R Kolesnick, E Gulbins
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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Sigma-Aldrich
Anti-Annexin V antibody, Mouse monoclonal, clone AN5, purified from hybridoma cell culture