溶解体中的LAMTOR-Rag复合体作为抗病毒干扰素生产的检查点
Zeming Feng1,2, Lulu Wang2,3, Shujun Chen2
1College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
The EMBO journal
|January 22, 2026
概括
溶解体通过通过LAMTOR-Rag GTPase通路控制I型干扰素 (IFN-β) 生产来调节抗病毒免疫力. 这种溶酶体检查点集成了代谢线索,协调免疫应对病毒感染的反应.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
背景情况:
- 溶解体越来越多地被认为是细胞防御机制中的关键信号平台.
- lysosomes 调节 I 型干扰素 (IFN-β) 产生的精确机制,这是一种关键的抗病毒细胞因子,仍然不完全理解.
- 模式识别受体 (PRR) 信号启动抗病毒反应,但下游溶酶体检查点是必不可少的.
研究的目的:
- 阐明 lysosome 的作用,特别是 LAMTOR-Rag GTPase 综合体在控制 IFN-β 生产中的作用.
- 为了确定链接 lysosomal 功能,营养感应和抗病毒免疫的分子机制.
- 为了在体内研究这种溶解体路径的生理意义.
主要方法:
- 在巨细胞中,LAMTOR或Rag GTPases的遗传移除.
- 对IFN-β产生和PRR信号的分析.
- 研究IRF表达和Ifnb1mRNA稳定性的研究.
- 评估p38 MAPK在溶酶体中的招募和酸化.
- 对Rag GTPase活性的营养可用性影响的评估.
- 在病毒感染模型中对LAMTOR-Rag-FLCN-p38轴的体外和体外研究.
主要成果:
- 一个以LAMTOR-Rag GTPase复合体为中心的溶解体通路被确定为IFN-β生产的关键.
- 对LAMTOR或Rag GTPase的遗传破坏取消了IFN-β反应,独立于PRR信号传递.
- 拉格GTPase活性调节IFN转录原始化的IRF表达.
- FLCN将p38 MAPK招募到溶酶体中,以进行Rag依赖酸化和Ifnb1mRNA稳定.
- 营养素的可用性动态控制Rag GTPase激活,将新陈代谢与IFN生产联系起来.
- 这个检查点独立于mTORC1.1.的功能.
结论:
- 溶酶体作为一个中央信号枢纽,整合了代谢和免疫线索来调节抗病毒防御.
- LAMTOR-Rag-FLCN-p38轴代表了IFN-β生产和抗病毒免疫的临界溶酶体特定检查点.
- 这一途径通过调节免疫反应,为病毒感染提供了潜在的治疗点.
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