VAMP-8 segregates mast cell-preformed mediator exocytosis from cytokine trafficking pathways
| Autor: | Wanjin Hong, Cheng-Chun Wang, Ulrich Blank, Zeng Qi, Gou Ke, Juan Rivera, Maria Rosa Soranzo, Neeraj Tiwari, Giuliano Zabucchi, Cristiana Brochetta, Francesca Vita |
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| Přispěvatelé: | Tiwari, N, WANG C., C, Brochetta, C, Ke, G, Vita, Francesca, Oi, Z, Rivera, J, Soranzo, MARIA ROSA, Zabucchi, Giuliano, Hang, W, Blank, U. |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Chemokine
medicine.medical_treatment Immunology mast cells Biology Immunoglobulin E Biochemistry Membrane Fusion Exocytosis Cell Degranulation R-SNARE Proteins Lactones Mice exocytosis cytokines inflammation medicine cytokine Animals exocytosi Antigens Anaphylaxis Mice Knockout Ionophores Qa-SNARE Proteins Ionomycin Secretory Vesicles Degranulation Munc-18 Cell Biology Hematology Qb-SNARE Proteins Mast cell Cell biology Protein Transport medicine.anatomical_structure Cytokine biology.protein Thapsigargin Tumor necrosis factor alpha mast cell Lysosomes Histamine |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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