Miao Yuxuan, Wu Jianxuan, Abraham Soman N
Department of Molecular Genetics & Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Immunity. 2016 Jul 19;45(1):94-105. doi: 10.1016/j.immuni.2016.06.023.
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. Although 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.
尽管细胞内运输系统对大多数生理活动不可或缺，但其在介导对感染的免疫反应中的作用仍不明确。在此，我们报告受感染的膀胱上皮细胞（BEC）动员外排体复合物（一种强大的亚细胞囊泡输出器），以迅速将细胞内细菌排出以进行清除。发现来自含细菌囊泡（BCV）的Toll样受体（TLR）4信号触发TRAF3在Lys168处发生K33连接的多聚泛素化，然后由鸟嘌呤核苷酸交换因子（GEF）RalGDS检测到，RalGDS促使外排体复合物组装。虽然TRAF3的这种独特修饰有助于将先天免疫信号传导与细胞运输装置联系起来，但它在确定众多亚细胞囊泡中哪些被识别并被选择以响应先天免疫信号进行排出方面，至关重要地确保了时间和空间的准确性。
