阶段分离驱动RNA病毒诱导的NLRP6炎症体的激活
Chen Shen1, Runzhi Li2, Roberto Negro3
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
在与dsRNA相互作用时,NLRP6蛋白经历液态分离 (LLPS),这对于炎症酶激活和对病毒和细菌的防御至关重要.
科学领域:
- 免疫学
- 分子生物学
- 细胞生物学
背景情况:
- NLRP6是宿主防御的关键调节者,调节炎酶激活和干扰素的产生.
- 了解NLRP6功能的分子机制对于开发抗微生物感染的策略至关重要.
研究的目的:
- 研究液态相分离 (LLPS) 在NLRP6介导宿主防御中的作用.
- 确定涉及NLRP6LLPS和炎症酶激活的特定序列和相互作用.
主要方法:
- 在体外和细胞检测中观察NLRP6LLPS.
- 针对位点的突变发生,以研究聚氨酸序列 (K350-354) 的功能.
- 使用感染病毒或受微生物群刺激的NLRP6缺乏和突变小鼠的体内研究.
主要成果:
- 在实验室和细胞中,NLRP6与双链RNA (dsRNA) 相互作用时发生LLPS.
- 在NLRP6中存在固有失序的多氨酸序列 (K350-354),对于多价值相互作用,LLPS和炎症酶激活至关重要.
- 缺乏NLRP6或突变的小鼠在病毒感染和肠道微生物群的反应中表现出减少的炎症酶激活,突出显示NLRP6LLPS在抗菌免疫中的作用.
- 通过螺旋组合招募ASC稳定NLRP6凝聚物,导致caspase-1激活.
- 利波泰可酸和DHX15也促进NLRP6LLPS,这表明NLRP6激活的常见机制.
结论:
- 作为对各种微生物配体的反应,NLRP6 LLPS是启动炎酶激活和干扰素生成的基本机制.
- 对于有效的抗微生物免疫力来说,NLRP6 接受LLPS的能力至关重要.
- NLRP6 LLPS 作为一个集成不同信号通路的平台,根据细胞环境指导不同的功能结果.
更多相关视频
06:52Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
12:43Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE
Published on: July 29, 2014
相关概念视频
Leaky Scanning
RNA Interference
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
siRNA - Small Interfering RNAs
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
Viruses with RNA Genomes
Transcription Initiation
The promoters and enhancers and their accessory proteins allow tight regulation of...
piRNA - Piwi-interacting RNAs
