Palmitoylation is required for efficient Fas cell death signaling.
Localization of the death receptor Fas to specialized membrane microdomains is crucial to Fas-mediated cell death signaling. Here, we report that the post-translational modification of Fas by palmitoylation at the membrane proximal cysteine residue in the cytoplasmic region is the targeting signal for Fas localization to lipid rafts, as demonstrated in both cell-free and living cell systems. Palmitoylation is required for the redistribution of Fas to actin cytoskeleton-linked rafts upon Fas stimulation and for the raft-dependent, ezrin-mediated cytoskeleton association, which is necessary for the efficient Fas receptor internalization, death-inducing signaling complex assembly and subsequent caspase cascade leading to cell death.
Chakrabandhu
Krittalak
K
Equipe labelisée La Ligue, Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Nice, France.
Hérincs
Zoltán
Z
Huault
Sébastien
S
Dost
Britta
B
Peng
Ling
L
Conchonaud
Fabien
F
Marguet
Didier
D
He
Hai-Tao
HT
Hueber
Anne-Odile
AO
D000595:Amino Acid Sequence; D000818:Animals; D016923:Cell Death; D003598:Cytoskeletal Proteins / Q000737:chemistry; D003599:Cytoskeleton / Q000378:metabolism; D053222:Fas Ligand Protein / Q000737:chemistry; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D019308:Palmitic Acid / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D019014:fas Receptor / Q000737:chemistry*; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D053222:Fas Ligand Protein; D019308:Palmitic Acid; D019014:fas Receptor; D000099149:Ezrin