TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity.
TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity.
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DOI：
10.1083/jcb.201503023
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发表时间：
2015-09-14
期刊：
影响因子：
--
通讯作者：
Deretic V
中科院分区：
文献类型：
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作者：
Kimura T;Jain A;Choi SW;Mandell MA;Schroder K;Johansen T;Deretic V
TRIM 20和TRIM 21是IFN-γ诱导的自噬的介质，其充当靶向特定炎性体组分的自噬受体调节剂和I型干扰素应答调节剂以通过精确自噬降解。目前哺乳动物细胞中选择性自噬的研究范式不能完全解释自噬降解的特异性和选择性。在本文中，我们报告了一个子集的三方基序（TRIM）蛋白作为专门的受体高度特异性自噬（精确自噬）的关键组成部分的炎性小体和I型干扰素反应系统。TRIM 20靶向炎性体组分，包括NLRP 3、NLRP 1和胱天蛋白酶原1，用于自噬降解，而TRIM 21靶向IRF 3。TRIM 20和TRIM 21直接结合它们各自的货物，并招募自噬机制来执行降解。TRIM 20的自噬功能受家族性地中海热相关突变的影响。这些发现拓宽了TRIMs作为自噬受体调节剂执行特定细胞质靶点的精确自噬的概念。在TRIM 20和TRIM 21的情况下，精确自噬控制中枢信号传导机制和关键因子，炎性小体和I型干扰素，指导人类的主要先天免疫应答系统。
TRIM20 and TRIM21 are mediators of IFN-γ–induced autophagy, which act as autophagic receptor regulators that target specific inflammasome components and type I interferon response regulators for degradation by precision autophagy. The present paradigms of selective autophagy in mammalian cells cannot fully explain the specificity and selectivity of autophagic degradation. In this paper, we report that a subset of tripartite motif (TRIM) proteins act as specialized receptors for highly specific autophagy (precision autophagy) of key components of the inflammasome and type I interferon response systems. TRIM20 targets the inflammasome components, including NLRP3, NLRP1, and pro–caspase 1, for autophagic degradation, whereas TRIM21 targets IRF3. TRIM20 and TRIM21 directly bind their respective cargo and recruit autophagic machinery to execute degradation. The autophagic function of TRIM20 is affected by mutations associated with familial Mediterranean fever. These findings broaden the concept of TRIMs acting as autophagic receptor regulators executing precision autophagy of specific cytoplasmic targets. In the case of TRIM20 and TRIM21, precision autophagy controls the hub signaling machineries and key factors, inflammasome and type I interferon, directing cardinal innate immunity response systems in humans.