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

Publication date: 19 September 2017
Source:Cell Reports, Volume 20, Issue 12
Author(s): Michihiro Takahama, Mitsunori Fukuda, Norihiko Ohbayashi, Tatsuya Kozaki, Takuma Misawa, Toru Okamoto, Yoshiharu Matsuura, Shizuo Akira, Tatsuya Saitoh
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.

Graphical abstract

Teaser

Takahama et al. show that RAB2B GTPase recruits its effector protein GARIL5 into the Golgi apparatus to positively regulate cytosolic DNA-triggered activation of the cGAS-STING signaling axis and promotes the type I IFN-mediated host defense response to DNA viruses.


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