Volume 24, No 8, Aug 2014
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 24 Issue 8, August 2014: 912-924 | Open Access
ORIGINAL ARTICLES
Dapper1 promotes autophagy by enhancing the Beclin1-Vps34-Atg14L complex formation
Benyu Ma1,*, Weipeng Cao1,4,*, Wenxia Li1, Chan Gao1, Zhen Qi1, Yan Zhao2, Jun Du1, Hua Xue1, Junya Peng1, Jun Wen1, Hua Chen1, Yuanheng Ning1, Lei Huang1, Hong Zhang2, Xiang Gao3, Li Yu1 and Ye-Guang Chen1
1State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
2State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
3Key Laboratory of Model Animal for Disease Study of Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China
4Current address: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China
Correspondence: Ye-Guang Chen, Tel: +86 10 6279 5184; Fax: +86 10 6279 4376(ygchen@tsinghua.edu.cn)
Autophagy is an intracellular degradation process to clear up aggregated proteins or aged and damaged organelles. The Beclin1-Vps34-Atg14L complex is essential for autophagosome formation. However, how the complex formation is regulated is unclear. Here, we show that Dapper1 (Dpr1) acts as a critical regulator of the Beclin1-Vps34-Atg14L complex to promote autophagy. Dpr1 ablation in the central nervous system results in motor coordination defect and accumulation of p62 and ubiquitinated proteins. Dpr1 increases autophagosome formation as indicated by elevated puncta formation of LC3, Atg14L and DFCP1 (Double FYVE-containing protein 1). Conversely, loss of Dpr1 impairs LC3 lipidation and causes p62/SQSTM1 accumulation. Dpr1 directly interacts with Beclin1 and Atg14L and enhances the Beclin1-Vps34 interaction and Vps34 activity. Together, our findings suggest that Dpr1 enhances the Atg14L-Beclin1-Vps34 complex formation to drive autophagy.
10.1038/cr.2014.84
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