通过TAX1BP1指导的Golgiphagy对STING信号进行负反调节
Sujit Suklabaidya1, Suchitra Mohanty1,2, Irene E Reider1
1Department of Cell and Biological Systems, Penn State College School of Medicine, Hershey, PA, USA.
Nature communications
|February 11, 2026
概括
选择性自受体TAX1BP1通过促进STING降解来负面调节cGAS-STING通路. 缺少TAX1BP1会增加I型干扰素 (IFN) 的产生和炎症.
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:
- 循环GMP-AMP合成酶 (cGAS) 刺激干扰素基因 (STING) 途径对先天免疫至关重要,在检测细胞核DNA时启动I型干扰素 (IFN) 和炎症反应.
- STING的溶酶体降解是终止cGAS-STING信号的关键机制,但精确的调节过程仍然不清楚.
研究的目的:
- 确定STING降解的新型调节剂,并阐明它们在控制cGAS-STING通路激活中的作用.
- 调查选择性自在终止STING信号传递和戈尔吉器官平衡中的作用.
主要方法:
- 利用TAX1BP1缺乏的巨细胞来评估STING信号和I型IFN的产生.
- 研究了通过微自的STING降解机制及其与ESCRT-0复合体的相互作用.
- 研究了TAX1BP1和p62/SQSTM1在Golgi碎片化和随后的Golgiphagy中的作用.
主要成果:
- 巨细胞中TAX1BP1缺乏导致STING聚合,增强STING信号传递,增加I型IFN和细胞因子的产生.
- TAX1BP1通过将STING与HGS蛋白联系起来,通过微自促使STING降解.
- 刺激激活诱导戈尔吉器官胀和碎片化,这是通过TAX1BP1和p62/SQSTM1.1介导的Golgiphagy解决的.
结论:
- TAX1BP1通过促进通过微自的STING降解,作为cGAS-STING通路的负调节者.
- STING激活触发了戈尔吉分裂,其下调与戈尔吉法基相结合,以限制先天免疫反应.
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