Identification of a lysine-rich region of Fas as a raft nanodomain targeting signal necessary for Fas-mediated cell death |
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Authors: | Aurélie Rossin Rosana Kral Nadia Lounnas Sébastien Mailfert Didier Marguet Anne-Odile Hueber |
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Institution: | a Université de Nice Sophia-Antipolis, CNRS UMR 6543, Institute of Developmental Biology and Cancer Research, Equipe labelisée La Ligue, Nice, France b Centre d'Immunologie de Marseille Luminy, Université de la Méditerranée, Marseille, France c INSERM, U631, Marseille, France d CNRS, UMR 6102, Marseille, France |
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Abstract: | Fas interaction at the plasma membrane with its lipid and protein environment plays a crucial role in the early steps of Fas signalling induced by Fas ligand binding. Particularly, Fas localisation in the raft nanodomains, ezrin-mediated interaction with the actin cytoskeleton and subsequent internalization are critical steps in Fas-mediated cell death. We identified a lysine-rich region (LRR) in the cytoplasmic, membrane-proximal region of Fas as a key determinant modulating these initial events. Through a genetic approach, we demonstrate that Fas LRR represents another signal additional to palmitoylation targeting Fas to the raft nanodomains, and modulates Fas interaction with the cytoskeleton. |
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Keywords: | Fas receptor Raft nanodomains Cell death signalling Actin cytoskeleton |
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