CD95 Signaling via Ceramide-rich Membrane Rafts

作者：Heike Grassmé, Andreas Jekle, Andrea Riehle, Heinz Schwarz, Jürgen Berger, Konrad Sandhoff, Richard Kolesnick, Erich Gulbins · 发表于：Journal of Biological Chemistry · 年份：2001 · DOI：10.1074/jbc.m101207200 · 被引用次数：633 · 研究领域：Sphingolipid Metabolism and Signaling、Lipid Membrane Structure and Behavior、Erythrocyte Function and Pathophysiology

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.