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Cell Rep. 2017 Sep 19;20(12):2944-2954. doi: 10.1016/j.celrep.2017.08.085.

The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune Responses.

Author information

1
Division of Inflammation Biology, Institute for Enzyme Research, Tokushima University, Tokushima 770-8503, Japan; Laboratory of Host Defense, World Premier International Research Center Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
2
Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Miyagi 980-8578, Japan.
3
Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Miyagi 980-8578, Japan; Department of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki 305-8575, Japan.
4
Laboratory of Host Defense, World Premier International Research Center Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
5
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
6
Division of Inflammation Biology, Institute for Enzyme Research, Tokushima University, Tokushima 770-8503, Japan; Laboratory of Host Defense, World Premier International Research Center Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan. Electronic address: saitohtatsuya@tokushima-u.ac.jp.

Abstract

Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces the IFN antiviral response. However, the regulatory mechanisms that mediate cGAS-triggered signaling have not been fully explored. Here, we show the involvement of a small GTPase, RAB2B, and its effector protein, Golgi-associated RAB2B interactor-like 5 (GARIL5), in the cGAS-mediated IFN response. RAB2B-deficiency affects the IFN response induced by cytosolic DNA. Consistent with this, RAB2B deficiency enhances replication of vaccinia virus, a DNA virus. After DNA stimulation, RAB2B colocalizes with stimulator of interferon genes (STING), the downstream signal mediator of cGAS, on the Golgi apparatus. The GTP-binding activity of RAB2B is required for its localization on the Golgi apparatus and for recruitment of GARIL5. GARIL5 deficiency also affects the IFN response induced by cytosolic DNA and enhances replication of vaccinia virus. These findings indicate that the RAB2B-GARIL5 complex promotes IFN responses against DNA viruses by regulating the cGAS-STING signaling axis.

KEYWORDS:

Rab GTPase; antiviral response; host defense; innate immunity; interferon; organelle

PMID:
28930687
PMCID:
PMC5614515
DOI:
10.1016/j.celrep.2017.08.085
[Indexed for MEDLINE]
Free PMC Article

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