Identification of a lysine-rich region of Fas as a raft nanodomain targeting signal necessary for Fas-mediated cell death

Exp Cell Res. 2010 May 15;316(9):1513-22. doi: 10.1016/j.yexcr.2010.03.002. Epub 2010 Mar 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Cytoskeleton / metabolism
  • Fas Ligand Protein
  • Fluorescent Antibody Technique
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Lipoylation
  • Lysine / chemistry
  • Lysine / genetics
  • Lysine / metabolism*
  • Membrane Microdomains / metabolism*
  • Mice
  • Mutation / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • T-Lymphocytes / metabolism
  • TNF-Related Apoptosis-Inducing Ligand / metabolism
  • fas Receptor / genetics
  • fas Receptor / metabolism*

Substances

  • Cytoskeletal Proteins
  • FAS protein, human
  • Fas Ligand Protein
  • Fas protein, mouse
  • RNA, Messenger
  • TNF-Related Apoptosis-Inducing Ligand
  • ezrin
  • fas Receptor
  • Lysine