The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune Responses.
The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune Responses.
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DOI：
10.1016/j.celrep.2017.08.085
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发表时间：
2017-09-19
期刊：
影响因子：
8.8
通讯作者：
Saitoh T
中科院分区：
文献类型：
--
作者：
Takahama M;Fukuda M;Ohbayashi N;Kozaki T;Misawa T;Okamoto T;Matsuura Y;Akira S;Saitoh T
环状GMP-AMP合成酶(CGAS)是一种胞内DNA感受器，可诱导干扰素的抗病毒反应。然而，介导cGAS触发的信号转导的调控机制还没有得到充分的探索。在这里，我们展示了一个小的GTP酶RAB2B及其效应蛋白高尔基相关的RAB2B相互作用器样5(GARIL5)参与了cGAS介导的干扰素反应。RAB2B缺陷影响胞浆DNA诱导的干扰素应答。与此一致的是，RAB2B缺乏会增强痘苗病毒的复制，牛痘病毒是一种DNA病毒。在DNA刺激后，RAB2B与cGAS下游的信号介质干扰素基因刺激物(STING)在高尔基体上共定位。RAB2B的GTP结合活性是其在高尔基体上定位和GARIL5招募所必需的。GARIL5缺乏也会影响胞浆DNA诱导的干扰素应答，并增强痘苗病毒的复制。这些发现表明，RAB2B-GARIL5复合体通过调节cGAS-STING信号轴促进干扰素对DNA病毒的应答。Takahama et al.结果表明，RAB2B GTPase将其效应蛋白GARIL5招募到高尔基体中，以正向调节胞浆DNA触发的cGAS-STING信号轴的激活，并促进I型干扰素介导的宿主对DNA病毒的防御反应。
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. 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. 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 type I IFN-mediated host defense response to DNA virus.
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影响因子：
8.7
作者：
Beutler B
通讯作者：
Beutler B
DOI：
10.1126/science.1244040
发表时间：
2013-09-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
Chen ZJ
影响因子：
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作者：
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通讯作者：
Sousa, Caetano Reis E.
影响因子：
64.8
作者：
Meylan, E;Curran, J;Tschopp, R
通讯作者：
Tschopp, R
影响因子：
30.5
作者：
Kawai, T;Takahashi, K;Akira, S
通讯作者：
Akira, S