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J. Biol. Chem., Vol. 276, Issue 23, 20589-20596, June 8, 2001
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,,
From the Department of Immunology, St. Jude Children's Research
Hospital, Memphis, Tennessee 38105, the § Kekulé
Institute for Organic Chemistry and Biochemistry, University of Bonn,
Gerhard-Domagk-Str.1, 53121 Bonn, the
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.
Max-Planck-Institute for Developmental Biology,
Spemannstrasse 35, 72076 Tuebingen, and the ¶ Laboratory of
Signal Transduction, Memorial Sloan-Kettering Cancer Center, New York,
New York 10021
To whom correspondence should be addressed: Dept. of
Immunology, St. Jude Children's Research Hospital, 332 North
Lauderdale, Memphis, TN 38105. Tel.: 901-495-3085; Fax: 901-495-3107;
E-mail: erich.gulbins@stjude.org.
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