Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 7, Pages 2580-2585Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0707854105
Keywords
serotonin; histamine; VAMP-8
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Funding
- Intramural NIH HHS Funding Source: Medline
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Mast cells degranulate and release the contents of intracellular secretory granules in response to the cross-linking of Fc epsilon RI by multivalent antigens. These granules contain a variety of biologically active inflammatory mediators; however, it is not clear whether these granules are homogenous or whether there is heterogeneity within the secretory granule population in mast cells. By using genetically altered mice lacking specific vesicle-associated SNARE membrane fusion proteins, we found that VAMP-8-deficient mast cells exhibited defects in Fc epsilon RI-regulated exocytosis, whereas synaptobrevin 2- or VAMP-3-deficient mast cells did not. Surprisingly, the defect in secretion in VAMP-8-deficient mice was limited to the subpopulation of mast cell secretory granules containing serotonin and cathepsin D, whereas regulated exocytosis of secretory granules containing histamine and TNF-alpha was normal. Confocal microscopy confirmed that serotonin and histamine were present in distinct intracellular granules and that most serotonin-containing granules were VAMP-8-positive. Thus, this study demonstrates that mast cells do indeed possess distinct subsets of secretory granules and that these subsets use different SNARE isoforms for exocytosis.
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