Zyxin stabilizes RIG-I and MAVS interactions and promotes type I interferon response.
Zyxin stabilizes RIG-I and MAVS interactions and promotes type I interferon response.
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DOI：
10.1038/s41598-017-12224-7
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发表时间：
2017-09-19
影响因子：
4.6
通讯作者：
Oshiumi H
中科院分区：
文献类型：
--
作者：
Kouwaki T;Okamoto M;Tsukamoto H;Fukushima Y;Matsumoto M;Seya T;Oshiumi H
RIG-I和MDA5是细胞质病毒RNA传感器，属于RIG-I样受体（rlr），可诱导抗病毒先天免疫反应，包括I型干扰素和其他促炎细胞因子的产生。在识别病毒RNA后，rig - 1和MDA5的n端caspase激活和募集域（CARD）与MAVS适配分子中的CARD结合，导致MAVS寡聚和下游信号传导。为了揭示MAVS依赖性信号转导的分子机制，我们进行了酵母双杂交筛选，并鉴定了酶是与MAVS结合的蛋白。Zyxin与MAVS在人细胞中共免疫沉淀。近端结扎实验表明，zyxin和MAVS在线粒体上部分共定位。异位表达的zyxin增强了mavs介导的IFN-β启动子的激活，而ZYX的敲低则减弱了IFN-β启动子的激活。此外，ZYX敲低可降低I型IFN和干扰素诱导基因在polyI:C或甲型流感病毒RNA刺激后的表达。有趣的是，RLRs和MAVS之间的物理相互作用被ZYX敲除。这些观察结果表明，zyxin是RLRs和MAVS相互作用的支架。
RIG-I and MDA5 are cytoplasmic viral RNA sensors that belong to the RIG-I-like receptors (RLRs), which induce antiviral innate immune responses, including the production of type I interferon and other pro-inflammatory cytokines. After recognition of viral RNA, the N-terminal caspase activation and recruitment domains (CARDs) of RIG-I and MDA5 bind to a CARD in the MAVS adaptor molecule, resulting in MAVS oligomerization and downstream signaling. To reveal the molecular mechanism of MAVS-dependent signaling, we performed a yeast two-hybrid screening and identified zyxin as a protein that binds to MAVS. Zyxin co-immunoprecipitated with MAVS in human cells. A proximity ligation assay showed that zyxin and MAVS partly co-localized on mitochondria. Ectopic expression of zyxin augmented MAVS-mediated IFN-β promoter activation, and knockdown of zyxin (ZYX) attenuated the IFN-β promoter activation. Moreover, ZYX knockdown reduced the expression of type I IFN and an interferon-inducible gene after stimulation with polyI:C or influenza A virus RNA. Interestingly, physical interactions between RLRs and MAVS were abrogated by ZYX knockdown. These observations indicate that zyxin serves as a scaffold for the interactions between RLRs and MAVS.
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影响因子：
32.4
作者：
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46.9
作者：
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DOI：
10.1083/jcb.149.5.1073
发表时间：
2000-05-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hirota T;Morisaki T;Nishiyama Y;Marumoto T;Tada K;Hara T;Masuko N;Inagaki M;Hatakeyama K;Saya H
通讯作者：
Saya H