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非自的Golgi-LC3脂化促进了TFE3应激反应,对抗Golgi功能障碍
Jaemin Kang1, Cathena Meiling Li1, Namhoon Kim2
1School of biological sciences, Seoul National University, Seoul, 08826, Korea.
The EMBO journal
|September 16, 2024
概括
对于戈尔吉应激反应至关重要的戈尔吉-LC3脂化是由戈尔吉后的贩运封锁引发的. 这一过程涉及ATG16L1和V-ATPase,对于TFE3核转移和适当的细胞防御至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 自学研究 自学研究
背景情况:
- 脂化ATG8/LC3蛋白对细胞功能至关重要,包括自.
- 在戈尔吉损伤后观察到戈尔吉-LC3脂化,但其在压力下的机制和作用尚不清楚.
研究的目的:
- 阐明在戈尔吉压力期间的戈尔吉-LC3脂化分子机制和功能.
- 调查DLK1过度表达在诱导高尔吉特异性LC3脂化中的作用.
主要方法:
- 利用DLK1的过度表达来诱导戈尔吉特异性的LC3脂化.
- 采用高尔基破坏性试剂来模仿细胞应激.
- 研究了ATG12-ATG5-ATG16L1复合体和V-ATPase相互作用的参与.
- 分析了LC3脂化对TFE3转位的影响.
主要成果:
- DLK1过度表达诱导了依赖ATG12-ATG5-ATG16L1复合体的Golgi-LC3脂化,主要是由Golgi后的贩运封锁引起的.
- 在戈尔吉压力期间,ATG16L1通过V-ATPase相互作用被招募到戈尔吉-LC3脂化中.
- 抑制高尔基后贩运导致TFE3的核转移,这是一个关键的高尔基压力调节器.
- 在LC3脂化中的缺陷损害了TFE3核转位,减弱了戈尔吉应激反应.
结论:
- 戈尔吉-LC3脂化与后戈尔吉贩运抑制和戈尔吉压力有机联系.
- 这种脂化过程在调节TFE3核转位和整体戈尔吉应激反应方面发挥着至关重要的作用.
- 这项研究揭示了Golgi-LC3脂化在压力下维持细胞平衡的尚未探索的功能.
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