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An essential role for membrane rafts in the initiation of Fas/CD95‐triggered cell death in mouse thymocytes
Author(s) -
Hueber AnneOdile,
Bernard AnneMarie,
Hérincs Zoltán,
Couzinet Arnaud,
He HaiTao
Publication year - 2002
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kvf022
Subject(s) - fadd , microbiology and biotechnology , death domain , lipid raft , fas receptor , fas ligand , caspase 8 , programmed cell death , apoptosis , biology , signal transduction , caspase , chemistry , biochemistry
Fas, a member of the tumor necrosis factor receptor family, can upon ligation by its ligand or agonistic antibodies trigger signaling cascades leading to cell death in lymphocytes and other cell types. Such signaling cascades are initiated through the formation of a membrane death‐inducing signaling complex (DISC) that includes Fas, the Fas‐associated death domain protein (FADD) and caspase‐8. We report here that a considerable fraction of Fas is constitutively partitioned into sphingolipid‐ and cholesterol‐rich membrane rafts in mouse thymocytes as well as the L12.10‐Fas T cells, and Fas ligation promotes a rapid and specific recruitment of FADD and caspase‐8 to the rafts. Raft disruption by cholesterol depletion abolishes Fas‐triggered recruitment of FADD and caspase‐8 to the membrane, DISC formation and cell death. Taken together, our results provide the first demonstration for an essential role of membrane rafts in the initiation of Fas‐mediated cell death signaling.