Atlastin 2/3 regulate ER targeting of the ULK1 complex to initiate autophagy |
| |
| Authors: | Nan Liu Hongyu Zhao Yan G Zhao Junjie Hu Hong Zhang |
| |
| Institution: | 1.National Laboratory of Biomacromolecules, Chinese Academy of Sciences Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People’s Republic of China;2.College of Life Sciences, University of Chinese Academy of Sciences, Beijing, People’s Republic of China;3.Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, People’s Republic of China |
| |
| Abstract: | 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. |
| |
| Keywords: | |
|
|
