Analysis of the Rab GTPase Interactome in Dendritic Cells Reveals Anti-microbial Functions of the Rab32 Complex in Bacterial Containment

Immunity
Yuanyuan LiYing Wan

Abstract

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.

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Citations

Sep 21, 2016·Small GTPases·Virtu Solano-ColladoStefania Spanò
Apr 22, 2017·Journal of Biochemistry·Norihiko OhbayashiYasunori Kanaho
Dec 15, 2017·Small GTPases·Marcellus J Banworth, Guangpu Li
Jul 3, 2019·The Journal of Experimental Medicine·Pengju OuCliff Y Yang
Aug 21, 2019·Cells·Noemi Antonella Guadagno, Cinzia Progida
May 7, 2020·Frontiers in Immunology·Zihao MiFuren Zhang
Oct 17, 2017·Frontiers in Cellular and Infection Microbiology·Akriti PrasharMaximiliano G Gutierrez
Apr 5, 2019·Journal of Immunology Research·Peiqing YangYi Liu
Jan 5, 2021·Frontiers in Cellular and Infection Microbiology·Arda BalciStefania Spanò

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