VAMP-8 segregates mast cell-preformed mediator exocytosis from cytokine trafficking pathways.

Author
Tiwari, Neeraj · Wang, Cheng-Chun · Brochetta, Cristiana · Ke, Gou · Vita, Francesca · Qi, Zeng · Rivera, Juan · Soranzo, Maria Rosa · Zabucchi, Giuliano · Hong, Wanjin · Blank, Ulrich
Published online 2008-01-18
Journal Blood
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Abstract

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.

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Details

Title
VAMP-8 segregates mast cell-preformed mediator exocytosis from cytokine trafficking pathways.
Author
Tiwari, Neeraj · Wang, Cheng-Chun · Brochetta, Cristiana · Ke, Gou · Vita, Francesca · Qi, Zeng · Rivera, Juan · Soranzo, Maria Rosa · Zabucchi, Giuliano · Hong, Wanjin · Blank, Ulrich
Published online
2008-01-18
Published
2008-04-01
Year
2008
Journal
Blood
Type*
Research Article
Language
eng
PMID
18203950
Keywords
Cell Degranulation · Immunology · Cytokines · Exocytosis · Mast Cells · Membrane Fusion · R-SNARE Proteins

Fields edited by Q-Sensei or Q-Sensei's users are marked with an asterisk (*).
This is Version 5 of this record. Anonymous user (IP:113.200.58.70) added this version on May 18, 2016. It is an edited version of the original data import from MEDLINE®/PubMed®. View changes to the previous version or view the complete version history.