Escherichia coli exposure inhibits exocytic SNARE-mediated membrane fusion in mast cells.
Escherichia coli exposure inhibits exocytic SNARE-mediated membrane fusion in mast cells.
复制标题
大肠杆菌暴露会抑制肥大细胞中胞吐 SNARE 介导的膜融合。
DOI：
10.1111/tra.12159
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Paumet,Fabienne
中科院分区：
文献类型：
--
作者：
Wesolowski,Jordan;Paumet,Fabienne
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 IKKβ 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 asEscherichia coli. However, the molecular mechanism(s) by which this occurs is unknown. Here, we show thatE. coliexposure rapidly and additively inhibits degranulation in the RBL‐2H3 rat mast cell line. Following co‐culture withE. coli, the interaction between IKKβ 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 thatE. coliexposure inhibits the formation of VAMP8‐containing exocytic SNARE complexes and thus the release of VAMP8‐dependent granules by interfering with SNAP23 phosphorylation.
