Analysis of the Rab GTPase Interactome in Dendritic Cells Reveals Anti-microbial Functions of the Rab32 Complex in Bacterial Containment
Analysis of the Rab GTPase Interactome in Dendritic Cells Reveals Anti-microbial Functions of the Rab32 Complex in Bacterial Containment
复制标题
树突状细胞中 Rab GTP 酶相互作用组的分析揭示了 Rab32 复合物在细菌遏制中的抗菌功能
DOI：
10.1016/j.immuni.2016.01.027
复制
发表时间：
2016-02-16
期刊：
影响因子：
32.4
通讯作者：
Wan, Ying
中科院分区：
文献类型：
--
作者：
Li, Yuanyuan;Wang, Yu;Wan, Ying
树突状细胞（DC）通过由Rab GTP酶连接在一起的相互连接的运输网络协调复杂的膜运输。通过串联亲和纯化策略和质谱分析，我们描绘了哺乳动物Rab GTdR家族主要成员的相互作用景观。当与成像工具互补时，这种蛋白质组学分析提供了细胞内膜组织的全局视图。在此基础上，我们研究了L.单核细胞增生性李斯特菌感染，并揭示了这个子网络在控制细胞内增殖的重要作用。单核细胞增多症在机制上，Rab 32与两个相互作用的蛋白质PHB和PHB 2形成持久的复合物，以在吞噬体形成早期和L.单核细胞增多症逃离了最初的容纳空泡。总的来说，我们提供了一个功能区室化的概述和细胞内Rab-mediated囊泡贩运的组织框架，可以作为未来调查的资源。
Dendritic cells (DCs) orchestrate complex membrane trafficking through an interconnected transportation network linked together by Rab GTPases. Through a tandem affinity purification strategy and mass spectrometry, we depicted an interactomic landscape of major members of the mammalian Rab GTPase family. When complemented with imaging tools, this proteomic analysis provided a global view of intracellular membrane organization. Driven by this analysis, we investigated dynamic changes to the Rab32 subnetwork in DCs induced by L. monocytogenes infection and uncovered an essential role of this subnetwork in controlling the intracellular proliferation of L. monocytogenes. Mechanistically, Rab32 formed a persistent complex with two interacting proteins, PHB and PHB2, to encompass bacteria both during early phagosome formation and after L. monocytogenes escaped the original containment vacuole. Collectively, we have provided a functional compartmentalization overview and an organizational framework of intracellular Rab-mediated vesicle trafficking that can serve as a resource for future investigations.