生物
炎症体
RNA沉默
核糖核酸
干扰素
细胞生物学
微生物学
分子生物学
受体
病毒学
RNA干扰
生物化学
基因
作者
Chen Shen,Runzhi Li,Roberto Negro,Jiewei Cheng,Setu M. Vora,Tian‐Min Fu,An Min Wang,Kaixin He,Liudmila Andreeva,Pu Gao,Zhigang Tian,Richard A. Flavell,Shu Zhu,Hao Wu
出处
期刊:Cell
[Elsevier]
日期:2021-11-01
卷期号:184 (23): 5759-5774.e20
被引量:91
标识
DOI:10.1016/j.cell.2021.09.032
摘要
NLRP6 is important in host defense by inducing functional outcomes including inflammasome activation and interferon production. Here, we show that NLRP6 undergoes liquid-liquid phase separation (LLPS) upon interaction with double-stranded RNA (dsRNA) in vitro and in cells, and an intrinsically disordered poly-lysine sequence (K350-354) of NLRP6 is important for multivalent interactions, phase separation, and inflammasome activation. Nlrp6-deficient or Nlrp6K350-354A mutant mice show reduced inflammasome activation upon mouse hepatitis virus or rotavirus infection, and in steady state stimulated by intestinal microbiota, implicating NLRP6 LLPS in anti-microbial immunity. Recruitment of ASC via helical assembly solidifies NLRP6 condensates, and ASC further recruits and activates caspase-1. Lipoteichoic acid, a known NLRP6 ligand, also promotes NLRP6 LLPS, and DHX15, a helicase in NLRP6-induced interferon signaling, co-forms condensates with NLRP6 and dsRNA. Thus, LLPS of NLRP6 is a common response to ligand stimulation, which serves to direct NLRP6 to distinct functional outcomes depending on the cellular context.
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