Atlastin 2/3 regulate ER targeting of the ULK1 complex to initiate autophagy

Liu, Nan1,2; Zhao, Hongyu1; Zhao, Yan G.3; Hu, Junjie1,2; Zhang, Hong1,2

2021-07-05

10.1083/jcb.202012091

JOURNAL OF CELL BIOLOGY   影响因子和分区

0021-9525

1540-8140

Dynamic targeting of the ULK1 complex to the ER is crucial for initiating autophagosome formation and for subsequent formation of ER-isolation membrane (IM; autophagosomal precursor) contact during IM expansion. Little is known about how the ULK1 complex, which comprises FIP200, ULK1, ATG13, and ATG101 and does not exist as a constitutively coassembled complex, is recruited and stabilized on the ER. Here, we demonstrate that the ER-localized transmembrane proteins Atlastin 2 and 3 (ATL2/3) contribute to recruitment and stabilization of ULK1 and ATG101 at the FIP200-ATG13-specified autophagosome formation sites on the ER. In ATL2/3 KO cells, formation of FIP200 and ATG13 puncta is unaffected, while targeting of ULK1 and ATG101 is severely impaired. Consequently, IM initiation is compromised and slowed. ATL2/3 directly interact with ULK1 and ATG13 and facilitate the ATG13-mediated recruitment/stabilization of ULK1 and ATG101. ATL2/3 also participate in forming ER-IM tethering complexes. Our study provides insights into the dynamic assembly of the ULK1 complex on the ER for autophagosome formation.

SCI

英语

NI论文

其他

National Natural Science Foundation of China[92054301,31630048,31790403] ; Chinese Ministry of Science and Technology[2017YFA0503401] ; Beijing Municipal Science and Technology Commission[Z181100001318003] ; Chinese Academy of Sciences[XDB19000000] ; Key Research Program of Frontier Sciences, Chinese Academy of Sciences[QYZDY-SSW-SMC006]

Cell Biology

Cell Biology

WOS:000654872300001

ROCKEFELLER UNIV PRESS

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Chinese Acad Sci, Ctr Excellence Biomacromol, Inst Biophys, Natl Lab Biomacromol, Beijing, Peoples R China
2.Univ Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China
3.Southern Univ Sci & Technol, Sch Life Sci, Dept Biol, Shenzhen, Peoples R China

Liu, Nan,Zhao, Hongyu,Zhao, Yan G.,et al. Atlastin 2/3 regulate ER targeting of the ULK1 complex to initiate autophagy[J]. JOURNAL OF CELL BIOLOGY,2021,220(7).

Liu, Nan,Zhao, Hongyu,Zhao, Yan G.,Hu, Junjie,&Zhang, Hong.(2021).Atlastin 2/3 regulate ER targeting of the ULK1 complex to initiate autophagy.JOURNAL OF CELL BIOLOGY,220(7).

Liu, Nan,et al."Atlastin 2/3 regulate ER targeting of the ULK1 complex to initiate autophagy".JOURNAL OF CELL BIOLOGY 220.7(2021).