通过Ragulator-Rag-mTORC1路径控制气体皮质D的寡合化和烧灭
Charles L Evavold1, Iva Hafner-Bratkovič2, Pascal Devant1
1Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Cell
|July 21, 2021
概括
在细胞死亡过程中,Ragulator-Rag复合体对气皮D (GSDMD) 孔隙形成至关重要. 这一发现将免疫调节与细胞代谢联系在一起.
科学领域:
- 免疫学
- 细胞生物学
- 分子生物学
背景情况:
- 细胞灭绝是免疫系统的重要途径.
- 炎症体和气皮D (GSDMD) 是热的关键媒介.
- 虽然GSDMD裂变已得到充分研究,但其下游孔隙形成的机制尚不清楚.
研究的目的:
- 确定气皮D (GSDMD) 孔隙形成所需的新型蛋白质.
- 阐明控制 GSDMD 介导的热的分子机制.
主要方法:
- 在巨细胞中进行基因查.
- 生物化学测定以评估GSDMD裂变,寡合化和孔隙形成.
- 对反应性氧物种 (ROS) 生产的分析.
主要成果:
- 该Ragulator-Rag复合体被确定为GSDMD毛孔形成和热的重要组成部分.
- 虽然Ragulator-Rag不参与GSDMD的裂变,但它促进了GSDMD在血上的寡合化.
- 增加活性氧物种 (ROS) 的线粒体毒素可以挽救GSDMD孔隙形成缺陷.
结论:
- 在GSDMD孔隙形成中,Ragulator-Rag复合体起着至关重要的,以前未知的作用.
- 反应性氧物种 (ROS) 是GSDMD孔隙组合的重要调节者.
- 这项研究揭示了免疫信号通路与新陈代谢调节之间的新联系.
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