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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3665-3674. Prepublished online as a Blood First Edition Paper on January 18, 2008; DOI 10.1182/blood-2007-07-103309. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-07-103309v1 111/7/3665    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 Citing Articles via Google Scholar Google Scholar Articles by Tiwari, N. Articles by Blank, U. Search for Related Content PubMed PubMed Citation Articles by Tiwari, N. Articles by Blank, U. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY VAMP-8 segregates mast cell–preformed mediator exocytosis from cytokine trafficking pathways Neeraj Tiwari1,2, Cheng-Chun Wang3, Cristiana Brochetta1,2, Gou Ke3, Francesca Vita4, Zeng Qi3, Juan Rivera5, Maria Rosa Soranzo4, Giuliano Zabucchi4, Wanjin Hong3, and Ulrich Blank1,2 1 Inserm U699, Paris, France; 2 Université Paris 7-Denis Diderot, Faculté de Médecine, Site Xavier Bichat, Paris, France; 3 Membrane Biology Laboratory, Institute of Molecular and Cellular Biology, Proteos, Singapore; 4 Department of Physiology and Pathology, University of Trieste, Trieste, Italy; and 5 Laboratory of Immune Cell Signaling, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD Inflammatory responses by mast cells are characterized by massive exocytosis of prestored granular mediators followed by cytokine/chemokine release. The vesicular trafficking mechanisms involved remain poorly understood. Vesicular-associated membrane protein-8 (VAMP-8), a member of the soluble N-ethylmaleimide–sensitive factor (NSF) attachment protein receptor (SNARE) family of fusion proteins initially characterized in endosomal and endosomal-lysosomal fusion, may also function in regulated exocytosis. Here we show that in bone marrow–derived mast cells (BMMCs) VAMP-8 partially colocalized with secretory granules and redistributed upon stimulation. This was associated with increased SNARE complex formation with the target t-SNAREs, SNAP-23 and syntaxin-4. VAMP-8–deficient BMMCs exhibited a markedly reduced degranulation response after IgE+ antigen-, thapsigargin-, or ionomycin-induced stimulation. VAMP-8–deficient mice also showed reduced plasma histamine levels in passive systemic anaphylaxis experiments, while cytokine/chemokine release was not affected. Unprocessed TNF accumulated at the plasma membrane where it colocalized with a VAMP-3–positive vesicular compartment but not with VAMP-8. The findings demonstrate that VAMP-8 segregates secretory lysosomal granule exocytosis in mast cells from cytokine/chemokine molecular trafficking pathways. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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