The dynamic interacting landscape of MAPL reveals essential functions for SUMOylation in innate immunity.
The dynamic interacting landscape of MAPL reveals essential functions for SUMOylation in innate immunity.
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DOI：
10.1038/s41598-017-00151-6
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发表时间：
2017-03-07
影响因子：
4.6
通讯作者：
McBride HM
中科院分区：
文献类型：
--
作者：
Doiron K;Goyon V;Coyaud E;Rajapakse S;Raught B;McBride HM
dsRNA 病毒触发的先天免疫反应的激活是通过线粒体抗病毒信号传导 (MAVS) 复合物的组装而发生的。识别病毒 dsRNA 后，胞质受体 RIG-I 被激活并招募到 MAVS 以激活免疫信号反应。我们在这里证明了在体内和体外驱动仙台病毒感染下游抗病毒基因转录激活的信号事件中对线粒体锚定蛋白连接酶 MAPL（也称为 MUL1）的严格要求。 MAPL 相互作用多肽的生物素环境扫描鉴定了一系列仙台病毒感染特异的蛋白质；包括 RIG-I、IFIT1、IFIT2、HERC5 等。感染后，RIG-I 以 MAPL 依赖性方式进行 SUMO 化，这是其激活所需的缀合步骤。与此一致的是，组成型激活形式的 RIG-I 的下游信号传导不需要 MAPL。这些数据强调了 MAPL 和线粒体 SUMO 化在抗病毒信号传导早期步骤中的关键作用。
Activation of the innate immune response triggered by dsRNA viruses occurs through the assembly of the Mitochondrial Anti-Viral Signaling (MAVS) complex. Upon recognition of viral dsRNA, the cytosolic receptor RIG-I is activated and recruited to MAVS to activate the immune signaling response. We here demonstrate a strict requirement for a mitochondrial anchored protein ligase, MAPL (also called MUL1) in the signaling events that drive the transcriptional activation of antiviral genes downstream of Sendai virus infection, both in vivo and in vitro. A biotin environment scan of MAPL interacting polypeptides identified a series of proteins specific to Sendai virus infection; including RIG-I, IFIT1, IFIT2, HERC5 and others. Upon infection, RIG-I is SUMOylated in a MAPL-dependent manner, a conjugation step that is required for its activation. Consistent with this, MAPL was not required for signaling downstream of a constitutively activated form of RIG-I. These data highlight a critical role for MAPL and mitochondrial SUMOylation in the early steps of antiviral signaling.