Article
- The EMBO Journal (2007) 26, 209 - 220
- doi:10.1038/sj.emboj.7601456
Published online: 7 December 2006
Subject Categories:
Palmitoylation is required for efficient Fas cell death signaling
Krittalak Chakrabandhu1,a, Zoltán Hérincs1,a, Sébastien Huault1, Britta Dost1, Ling Peng2, Fabien Conchonaud3,4,5, Didier Marguet3,4,5, Hai-Tao He3,4,5 and Anne-Odile Hueber1
- Equipe labelisée La Ligue, Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Nice, France
- CNRS UMR 6114, Département de Chimie, Marseille, France
- Centre d'Immunologie de Marseille Luminy, Université de la Méditerranée, Marseille, France
- INSERM, UMR 631, Marseille, France
- CNRS, UMR 6102, Marseille, France
Correspondence to:
Anne-Odile Hueber, Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre A Lacassagne, 33, Avenue de Valombrose, 06189 Nice, France. Tel.: +33 492 031241; Fax: +33 492 031245; E-mail: hueber@unice.fr
aThese authors contributed equally to this work
Received 12 May 2006; Accepted 29 September 2006
Abstract
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.
Keywords:
- cell death,
- Fas,
- palmitoylation,
- rafts,
- signal transduction
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