Dapper1 promotes autophagy by enhancing the Beclinl -Vps34-Atg14L complex formation  

作　　者：Benvu Ma Weipeng Cao Wenxia Li Chan Gao Zhen Qi Yan Zhao Jun Du Hua Xue Junya Peng Jun Wen Hua Chen Yuanheng Ning Lei Huang Hong Zhang Xiang Gao Li Yu Ye-Guang Chen 

机构地区：[1]State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China [2]State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chi- nese Academy of Sciences, Beijing 100101, China [3]Key Laboratory of Model Animal for Disease Study of Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China [4]CAS Key Laboratory for Biomedical Effects of Nanoma-tedals and Nanosafety, National Center for Nanoscience and Technology,Beijing 100190, China

出　　处：《Cell Research》2014年第8期912-924,共13页细胞研究（英文版）

摘　　要：Autophagy is an intracellular degradation process to clear up aggregated proteins or aged and damaged organelles. The Beclinl-Vps34-Atg14L complex is essential for autophagosome formation. However, how the complex formation is regulated is unclear. Here, we show that Dapperl （Dprl） acts as a critical regulator of the Beclinl-Vps34-Atg14L complex to promote autophagy. Dprl ablation in the central nervous system results in motor coordination defect and accumulation of p62 and ubiquitinated proteins. Dprl increases autophagosome formation as indicated by elevated puncta formation of LC3, Atg14L and DFCP1 （Double FYVE-containing protein 1）. Conversely, loss of Dprl impairs LC3 lipidation and causes p62/SQSTM1 accumulation. Dprl directly interacts with Beclinl and Atg14L and enhances the Beclinl-Vps34 interaction and Vps34 activity. Together, our findings suggest that Dprl enhances the Atg14L-Beclinl-Vps34 complex formation to drive autophagy.

关 键 词：AUTOPHAGY BECLINL Dapperl NEURODEGENERATION Vps34 

分 类 号：Q945.11[生物学—植物学] Q523