VAMP-8 segregates mast cell–preformed mediator exocytosis from cytokine trafficking pathways
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- Neeraj Tiwari
- Inserm U699, Paris, France;
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- Cheng-Chun Wang
- Membrane Biology Laboratory, Institute of Molecular and Cellular Biology, Proteos, Singapore;
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- Cristiana Brochetta
- Inserm U699, Paris, France;
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- Gou Ke
- Membrane Biology Laboratory, Institute of Molecular and Cellular Biology, Proteos, Singapore;
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- Francesca Vita
- Department of Physiology and Pathology, University of Trieste, Trieste, Italy; and
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- Zeng Qi
- Membrane Biology Laboratory, Institute of Molecular and Cellular Biology, Proteos, Singapore;
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- Juan Rivera
- Laboratory of Immune Cell Signaling, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD
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- Maria Rosa Soranzo
- Department of Physiology and Pathology, University of Trieste, Trieste, Italy; and
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- Giuliano Zabucchi
- Department of Physiology and Pathology, University of Trieste, Trieste, Italy; and
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- Wanjin Hong
- Membrane Biology Laboratory, Institute of Molecular and Cellular Biology, Proteos, Singapore;
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- Ulrich Blank
- Inserm U699, Paris, France;
書誌事項
- 公開日
- 2008-04-01
- DOI
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- 10.1182/blood-2007-07-103309
- 公開者
- American Society of Hematology
この論文をさがす
説明
<jats:title>Abstract</jats:title><jats:p>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.</jats:p>
収録刊行物
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- Blood
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Blood 111 (7), 3665-3674, 2008-04-01
American Society of Hematology
