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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2384-2391. Prepublished online as a Blood First Edition Paper on November 10, 2005; DOI 10.1182/blood-2005-07-2883. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-07-2883v1 107/6/2384    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cahuzac, N. Articles by Hueber, A.-O. Search for Related Content PubMed PubMed Citation Articles by Cahuzac, N. Articles by Hueber, A.-O. Related Collections Immunobiology Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Fas ligand is localized to membrane rafts, where it displays increased cell death–inducing activity Nathalie Cahuzac, Wiebke Baum, Vladimir Kirkin, Fabien Conchonaud, Laure Wawrezinieck, Didier Marguet, Ottmar Janssen, Martin Zörnig, and Anne-Odile Hueber From the Equipe labelisée La Ligue; Institute of Signaling, Developmental Biology and Cancer Research, Nice, France CNRS UMR 6543; Chemotherapeutisches Forschungsinstitut, Frankfurt, Germany; Centre d'Immunologie de Marseille Luminy, Université de la Méditerranée, Marseille, France; and Institute of Immunology, University Hospital Schleswig-Holstein, Campus Kiel, Germany. Fas ligand (FasL), a member of the TNF protein family, potently induces cell death by activating its matching receptor Fas. Fas-mediated killing plays a critical role in naturally and pathologically occurring cell death, including development and homeostasis of the immune system. In addition to its receptor-interacting and cell death–inducing extracellular domain, FasL has a well-conserved intracellular portion with a proline-rich SH3 domain–binding site probably involved in non-apoptotic functions. We report here that, as with the Fas receptor, a fraction of FasL is constitutively localized in rafts. These dynamic membrane microdomains, enriched in sphingolipids and cholesterol, are important for cell signaling and trafficking processes. We show that FasL is partially localized in rafts and that increased amounts of FasL are found in rafts after efficient FasL/Fas receptor interactions. Raft disorganization after cholesterol oxidase treatment and deletions within the intracellular FasL domain diminish raft partitioning and, most important, lead to decreased FasL killing. We conclude that FasL is recruited into lipid rafts for maximum Fas receptor contact and cell death–inducing potency. These findings raise the possibility that certain pathologic conditions may be treated by altering the cell death–inducing capability of FasL with drugs affecting its raft localization. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Le Lay, Q. Li, N. Proschogo, M. Rodriguez, K. Gunaratnam, S. Cartland, C. Rentero, W. Jessup, T. Mitchell, and K. Gaus Caveolin-1-dependent and -independent membrane domains J. Lipid Res., August 1, 2009; 50(8): 1609 - 1620. [Abstract] [Full Text] [PDF] N. Engedal, P. Auberger, and H. K. Blomhoff Retinoic acid regulates Fas-induced apoptosis in Jurkat T cells: reversal of mitogen-mediated repression of Fas DISC assembly J. Leukoc. Biol., March 1, 2009; 85(3): 469 - 480. [Abstract] [Full Text] [PDF] A. Ginouves, K. Ilc, N. Macias, J. Pouyssegur, and E. Berra PHDs overactivation during chronic hypoxia "desensitizes" HIF{alpha} and protects cells from necrosis PNAS, March 25, 2008; 105(12): 4745 - 4750. [Abstract] [Full Text] [PDF] J. Huang, L. J. Edwards, B. D. Evavold, and C. Zhu Kinetics of MHC-CD8 Interaction at the T Cell Membrane J. Immunol., December 1, 2007; 179(11): 7653 - 7662. [Abstract] [Full Text] [PDF] M. Sun, S. Lee, S. Karray, M. Levi-Strauss, K. T. Ames, and P. J. Fink Cutting Edge: Two Distinct Motifs within the Fas Ligand Tail Regulate Fas Ligand-Mediated Costimulation J. Immunol., November 1, 2007; 179(9): 5639 - 5643. [Abstract] [Full Text] [PDF]

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