TFEB将cGAS-STING通路与溶酶体生物发生联系起来
Yaping Meng1, Xinran Li2, Haoxing Xu3
1New Cornerstone Science Laboratory and Liangzhu Laboratory, the Second Affiliated Hospital and School of Basic Medical Sciences, Zhejiang University, Hangzhou, China.
Trends in cell biology
|November 15, 2024
概括
循环GMP-AMP合成酶 (cGAS) 刺激干扰素基因 (STING) 途径对于先天免疫非常重要. STING激活还通过将转录因子TFEB/TFE3移动到核中,独立于TBK1促进了 lysosomal生物发生.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 循环GMP-AMP合成酶 (cGAS) 刺激干扰素基因 (STING) 途径是天生的免疫系统的关键组成部分.
- 这一途径检测细胞质双链DNA (dsDNA),并激活免疫反应,主要是通过效应酶TBK1.
研究的目的:
- 为了研究STING激活超出TBK1-介导免疫的下游效应.
- 确定STING信号是否会影响其他细胞过程,例如有机体生物发生.
主要方法:
- 该研究使用基于细胞的测试来监测STING通路的激活.
- 研究人员使用免疫光检测评估了转录因子TFEB和TFE3的局部化.
- 使用溶解体标记物和生物发生试验量化了溶解体形成.
主要成果:
- 发现STING激活诱导转录因子TFEB和TFE3.3的核转位.
- 这种核转移独立于正规的TBK1激活途径发生.
- TFEB/TFE3的核转位导致了 lysosomal生物发生的增加.
结论:
- 刺痛信号传递具有双重作用,调节先天免疫和溶酶体平衡.
- 通过TFEB/TFE3激活,cGAS-STING通路协调免疫防御与细胞维护.
- 这一发现揭示了一个新的机制,将DNA传感与 lysosomal 功能联系起来.
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