First Author | Puri N | Year | 2008 |
Journal | Proc Natl Acad Sci U S A | Volume | 105 |
Issue | 7 | Pages | 2580-5 |
PubMed ID | 18250339 | Mgi Jnum | J:131926 |
Mgi Id | MGI:3774824 | Doi | 10.1073/pnas.0707854105 |
Citation | Puri N, et al. (2008) Mast cells possess distinct secretory granule subsets whose exocytosis is regulated by different SNARE isoforms. Proc Natl Acad Sci U S A 105(7):2580-5 |
abstractText | Mast cells degranulate and release the contents of intracellular secretory granules in response to the cross-linking of FcepsilonRI by multivalent antigens. These granules contain a variety of biologically active inflammatory mediators; however, it is not clear whether these granules are homogeneous 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 FcepsilonRI-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. |