期刊
AUTOPHAGY
卷 15, 期 10, 页码 1774-1786出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2019.1596478
关键词
Autophagosome; autolysosome; GOLGA2; Golgi apparatus; RAB2; RUBCNL
类别
资金
- National Natural Science Foundation [91754113, 31771525, 31500627]
- Ministry of Science and Technology of the People's Republic of China [2017YFA0503402]
- Zhejiang provincial Funds for Distinguished Young Scientists [LR15C070001]
- Fundamental Research Funds for the Central Universities [2017FZA7014]
Multiple sources contribute membrane and protein machineries to construct functional macroautophagic/autophagic structures. However, the underlying molecular mechanisms remain elusive. Here, we show that RAB2 connects the Golgi network to autophagy pathway by delivering membrane and by sequentially engaging distinct autophagy machineries. In unstressed cells, RAB2 resides primarily in the Golgi apparatus, as evidenced by its interaction and colocalization with GOLGA2/GM130. Importantly, autophagy stimuli dissociate RAB2 from GOLGA2 to interact with ULK1 complex, which facilitates the recruitment of ULK1 complex to form phagophores. Intriguingly, RAB2 appears to modulate ULK1 kinase activity to propagate signals for autophagosome formation. Subsequently, RAB2 switches to interact with autophagosomal RUBCNL/PACER and STX17 to further specify the recruitment of HOPS complex for autolysosome formation. Together, our study reveals a multivalent pathway in bulk autophagy regulation, and provides mechanistic insights into how the Golgi apparatus contributes to the formation of different autophagic structures.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据