该cGAS-STING通路激活转录因子TFEB以刺激溶酶体生物发生和病原体清除
Yinfeng Xu1, Qian Wang2, Jun Wang3
1Laboratory of Basic Biology, Hunan First Normal University, Changsha 410205, Hunan, China.
Immunity
|December 17, 2024
概括
循环GMP-AMP (cGAMP) 合成酶 (cGAS) 刺激干扰素基因 (STING) 途径通过促进溶酶体生物生成来增强溶酶体活性. 这个过程有助于清除细胞碎片和病原体.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 已知循环GMP-AMP (cGAMP) 合成酶 (cGAS) 刺激干扰素基因 (STING) 途径可诱导货物降解的自.
- 对cGAS-STING通路对 lysosome 功能本身的影响在很大程度上仍未被探索.
研究的目的:
- 为了研究cGAS-STING通路是否调节 lysosome 功能.
- 阐明通过STING激活影响 lysosome活动和生物发生的机制.
主要方法:
- 分析STING激活对 lysosome生物生成的影响.
- 调查TFEB,TFE3和MITF核转移的作用.
- 检查GABARAP的脂化及其与FLCN/FNIP复合体的相互作用.
- 评估对mTORC1信号和TFEB酸化的影响.
主要成果:
- 杆激活通过刺激 lysosome 生物发生,独立于 TANK 结合激酶 1 (TBK1) 来上调 lysosomal 活动.
- STING诱导转录因子TFEB,TFE3和MITF的核转位.
- 在STING囊泡上由STING诱导的GABARAP脂化通过隔离FLCN/FNIP激活TFEB,抑制mTORC1依赖的TFEB失活.
- 通过STING介导的溶酶体生物发生促进了细胞质DNA和病原体的清除.
结论:
- 这种cGAS-STING通路在诱导 lysosome生物生成方面具有新的功能.
- 这种溶解体生物发生诱导对于细胞防御DNA和病原体至关重要.
- 通过 lysosomal 机制,STING 信号直接增强细胞降解能力.
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