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

Michihiro Takahama, Mitsunori Fukuda, Norihiko Ohbayashi, Tatsuya Kozaki, Takuma Misawa, Toru Okamoto, Yoshiharu Matsuura, Shizuo Akira, Tatsuya Saitoh

    Research output: Contribution to journalArticlepeer-review

    8 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)2944-2954
    Number of pages11
    JournalCell Reports
    Volume20
    Issue number12
    DOIs
    Publication statusPublished - 2017 Sep 19

    Keywords

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

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

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