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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wesolowski, Jordan Paumet, Fabienne |
| Description | Country affiliation: United States Author Affiliation: Wesolowski J ( Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA.) |
| Abstract | Mast cells orchestrate the allergic response through the release of proinflammatory mediators, which is driven by the fusion of cytoplasmic secretory granules with the plasma membrane. During this process, SNARE proteins including Syntaxin4, SNAP23 and VAMP8 play a key role. Following stimulation, the kinase IKKß interacts with and phosphorylates the t-SNARE SNAP23. Phosphorylated SNAP23 then associates with Syntaxin4 and the v-SNARE VAMP8 to form a ternary SNARE complex, which drives membrane fusion and mediator release. Interestingly, mast cell degranulation is impaired following exposure to bacteria such as Escherichia coli. However, the molecular mechanism(s) by which this occurs is unknown. Here, we show that E. coli exposure rapidly and additively inhibits degranulation in the RBL-2H3 rat mast cell line. Following co-culture with E. coli, the interaction between IKKß and SNAP23 is disrupted, resulting in the hypophosphorylation of SNAP23. Subsequent formation of the ternary SNARE complex between SNAP23, Syntaxin4 and VAMP8 is strongly reduced. Collectively, these results demonstrate that E. coli exposure inhibits the formation of VAMP8-containing exocytic SNARE complexes and thus the release of VAMP8-dependent granules by interfering with SNAP23 phosphorylation. |
| File Format | HTM / HTML |
| ISSN | 13989219 |
| e-ISSN | 16000854 |
| DOI | 10.1111/tra.12159 |
| Journal | Traffic |
| Issue Number | 5 |
| Volume Number | 15 |
| Language | English |
| Publisher | Wiley |
| Publisher Date | 2014-05-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Discipline Physiology Escherichia Coli Metabolism Mast Cells Physiology Membrane Fusion Snare Proteins Animals Cell Line Coculture Techniques I-kappa B Kinase Membrane Microdomains Membrane Proteins Phosphorylation Protein Binding Qa-snare Proteins R-snare Proteins Vesicular Transport Proteins Research Support, N.i.h., Extramural |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Genetics Structural Biology Molecular Biology Biochemistry |
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