Ubiquitination of Innate Immune Regulator TRAF3 Orchestrates Expulsion of Intracellular Bacteria by Exocyst Complex.
Ubiquitination of Innate Immune Regulator TRAF3 Orchestrates Expulsion of Intracellular Bacteria by Exocyst Complex.
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DOI：
10.1016/j.immuni.2016.06.023
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发表时间：
2016-07-19
期刊：
影响因子：
32.4
通讯作者：
Abraham SN
中科院分区：
文献类型：
--
作者：
Miao Y;Wu J;Abraham SN
尽管细胞内运输系统是大多数生理活动的组成部分，但其在介导对感染的免疫应答中的作用仍然难以捉摸。在这里，我们报告说，受感染的膀胱上皮细胞（BECs）动员外囊复合物，一个强大的出口商的亚细胞囊泡，迅速驱逐胞内细菌回来清除。Toll样受体（TLR）4信号从细菌含有囊泡（BCV）被发现触发K33连接的TRAF3在Lys168的多聚泛素化，然后检测到RalGDS，鸟嘌呤核苷酸交换因子（GEF），沉淀外囊复合物的装配。虽然TRAF3的这种独特修饰用于将先天免疫信号传导与细胞运输装置连接，但它在确定许多亚细胞囊泡中哪一个被识别并选择用于响应先天免疫信号传导而排出时至关重要地确保了时间和空间准确性。
Although the intracellular trafficking system is integral to most physiologic activities, its role in mediating immune responses to infection has remained elusive. Here, we report that infected bladder epithelial cells (BECs) mobilized the exocyst complex, a powerful exporter of subcellular vesicles, to rapidly expel intracellular bacteria back for clearance. Toll-like Receptor (TLR) 4 signals emanating from bacteria containing vesicles (BCVs) were found to trigger K33-linked polyubiquitination of TRAF3 at Lys168 which was then detected by RalGDS, a guanine nucleotide exchange factor (GEF) that precipitated the assembly of the exocyst complex. While this distinct modification of TRAF3 served to connect innate immune signaling to the cellular trafficking apparatus, it crucially ensured temporal and spatial accuracy in determining which among the many subcellular vesicles was recognized and selected for expulsion in response to innate immune signaling.