通过调节NLRP3炎症体,DDX3X在应激细胞中起到活死检查点的作用
Parimal Samir1, Sannula Kesavardhana1, Deanna M Patmore2
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Nature
|September 13, 2019
概括
细胞应激颗粒通过隔离DDX3X来抑制炎症酶激活,这是炎症酶组合至关重要的蛋白质. 这种机制有助于细胞通过压力颗粒生存或通过热死亡.
科学领域:
- 细胞生物学
- 免疫学
- 分子生物学
背景情况:
- 细胞应激反应调节平衡,压力颗粒促进生存,炎症细胞驱动炎症性细胞死亡 (热).
- 压力颗粒和炎症体,特别是NLRP3炎症体,是由细胞压力触发的,但会产生相反的结果.
- 在细胞命运决策中,压力颗粒和炎症体之间的相互作用仍然不太清楚.
研究的目的:
- 调查压力颗粒和NLRP3炎症体之间的交叉声.
- 阐明在压力条件下的细胞命运决定的分子机制.
- 确定参与协调这些途径的关键蛋白质.
主要方法:
- 研究了压力颗粒诱导对NLRP3炎症酶激活和热的作用.
- 使用共免疫沉来确定压力颗粒组件和炎症蛋白之间的蛋白质相互作用.
- 在体内检测了DDX3X在压力颗粒组合和炎症细胞激活中的作用.
主要成果:
- 压力颗粒的形成特别抑制了NLRP3炎症酶的激活,ASC斑块的组合和热.
- 压力颗粒蛋白DDX3X与NLRP3直接相互作用,并且需要用于炎症酶激活.
- 压力颗粒组合封存DDX3X,从而防止炎症酶激活并促进细胞存活.
- 在体内,DDX3X的损失或肌肉细胞中压力颗粒的诱导减少了依赖炎症细胞因子的产生.
结论:
- DDX3X作为一个分子开关,调解支持生存的压力颗粒和支持死亡的炎症体之间的竞争.
- 巨细胞利用DDX3X的可用性来解释压力信号,并做出生死细胞命运决定.
- 一个涉及DDX3X的类静态机制调节细胞命运,以应对细胞应激.
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