CD95 signaling via ceramide-rich membrane rafts.
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.
Grassme
H
H
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Jekle
A
A
Riehle
A
A
Schwarz
H
H
Berger
J
J
Sandhoff
K
K
Kolesnick
R
R
Gulbins
E
E
D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D013107:Sphingolipids / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
D002518:Ceramides; D013107:Sphingolipids; D019014:fas Receptor