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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2290-2299. Prepublished online as a Blood First Edition Paper on December 3, 2007; DOI 10.1182/blood-2007-06-096529. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-06-096529v1 111/4/2290    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 CrossRef Google Scholar Articles by Moretti, S. Articles by Catalano, A. PubMed PubMed Citation Articles by Moretti, S. Articles by Catalano, A. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Semaphorin3A signaling controls Fas (CD95)-mediated apoptosis by promoting Fas translocation into lipid rafts Simona Moretti1,2, Antonio Procopio1,2, Raffaella Lazzarini1,2, Maria Rita Rippo1,2, Roberto Testa3, Maurizio Marra3, Luca Tamagnone4, and Alfonso Catalano1,2 1 Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, Ancona; 2 Center of Cytology and 3 Diabetology Unit, Research Department, Italian National Research Centers on Aging, Ancona; and 4 Institute for Cancer Research and Treatment, University of Turin, Candiolo, Italy Semaphorins and their receptors (plexins) have pleiotropic biologic functions, including regulation of immune responses. However, the role of these molecules inside the immune system and the signal transduction mechanism(s) they use are largely unknown. Here, we show that Semaphorin3A (Sema3A) triggers a proapoptotic program that sensitizes leukemic T cells to Fas (CD95)-mediated apoptosis. We found that Sema3A stimulation provoked Fas translocation into lipid raft microdomains before binding with agonistic antibody or FasL (CD95L). Disruption of lipid rafts reduced sensitivity to Fas-mediated apoptosis in the presence of Sema3A. Furthermore, we show that plexin-A1, together with Sema3A-binding neuropilin-1, was rapidly incorporated into membrane rafts after ligand stimulation, resulting in the transport of actin-linking proteins into Fas-enriched rafts. Cells expressing a dominant-negative mutant of plexin-A1 did not show Fas clustering and apoptosis on Sema3A/Fas costimulation. This work identifies a novel biologic function of semaphorins and presents an unexpected signaling mechanism linking semaphorin to the tumor necrosis factor family receptors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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