LRRC25 inhibits type I IFN signaling by targeting ISG15-associated RIG-I for autophagic degradation
LRRC25 inhibits type I IFN signaling by targeting ISG15-associated RIG-I for autophagic degradation
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DOI：
10.15252/embj.201796781
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发表时间：
2018-02-01
期刊：
影响因子：
11.4
通讯作者：
Wang, Rong-Fu
中科院分区：
文献类型：
--
作者：
Du, Yang;Duan, Tianhao;Wang, Rong-Fu
RIG-I样受体(RLRs)对于抵抗RNA病毒感染至关重要，必须严格控制其活性以维持免疫平衡。在这里，我们报告了富含亮氨酸重复序列的蛋白25(LRRC25)是RLR介导的I型干扰素(IFN)信号的关键负调控因子。在RNA病毒感染后，LRRC25特异性地与ISG15相关的RIG-I结合，促进RIG-I与自噬货物受体p62之间的相互作用，并通过选择性自噬介导RIG-I的降解。LRRC25或ISG15的耗尽取消了RIG-I-p62的相互作用以及RIG-I的自噬降解。总之，我们的发现确认了LRRC25在I型干扰素信号激活中的一个先前未被认识的角色，通过LRRC25作为辅助受体帮助RIG-I以p62依赖的方式递送到自噬体内降解。
The RIG-I-like receptors (RLRs) are critical for protection against RNA virus infection, and their activities must be stringently controlled to maintain immune homeostasis. Here, we report that leucine-rich repeat containing protein 25 (LRRC25) is a key negative regulator of RLR-mediated type I interferon (IFN) signaling. Upon RNA virus infection, LRRC25 specifically binds to ISG15-associated RIG-I to promote interaction between RIG-I and the autophagic cargo receptor p62 and to mediate RIG-I degradation via selective autophagy. Depletion of either LRRC25 or ISG15 abrogates RIG-I-p62 interaction as well as the autophagic degradation of RIG-I. Collectively, our findings identify a previously unrecognized role of LRRC25 in type I IFN signaling activation by which LRRC25 acts as a secondary receptor to assist RIG-I delivery to autophagosomes for degradation in a p62-dependent manner.