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Dapper1通过增强Beclin1-Vps34-Atg14L复合物的形成来促进自噬。

Dapper1 promotes autophagy by enhancing the Beclin1-Vps34-Atg14L complex formation.

作者信息

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

机构信息

State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.

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] Current address: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China.

出版信息

Cell Res. 2014 Aug;24(8):912-24. doi: 10.1038/cr.2014.84. Epub 2014 Jul 1.

DOI:10.1038/cr.2014.84
PMID:24980960
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4123296/
Abstract

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.

摘要

自噬是一种细胞内降解过程，用于清除聚集的蛋白质或老化及受损的细胞器。Beclin1-Vps34-Atg14L复合物对于自噬体的形成至关重要。然而，该复合物的形成是如何被调控的尚不清楚。在此，我们表明Dapper1（Dpr1）作为Beclin1-Vps34-Atg14L复合物的关键调节因子来促进自噬。中枢神经系统中Dpr1的缺失导致运动协调缺陷以及p62和泛素化蛋白的积累。如LC3、Atg14L和DFCP1（含双FYVE结构域蛋白1）的点状结构增加所示，Dpr1增加自噬体的形成。相反，Dpr1的缺失会损害LC3脂化并导致p62/SQSTM1积累。Dpr1直接与Beclin1和Atg14L相互作用，并增强Beclin1-Vps34的相互作用以及Vps34的活性。总之，我们的研究结果表明Dpr1增强Atg14L-Beclin1-Vps34复合物的形成以驱动自噬。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95fa/4123296/90dc75cf8624/cr201484f6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95fa/4123296/13dc3068bd4d/cr201484f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95fa/4123296/1cd30c399863/cr201484f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95fa/4123296/0d76321c5191/cr201484f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95fa/4123296/90dc75cf8624/cr201484f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95fa/4123296/c018bfa94e19/cr201484f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95fa/4123296/9eeb25bac5d6/cr201484f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95fa/4123296/13dc3068bd4d/cr201484f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95fa/4123296/1cd30c399863/cr201484f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95fa/4123296/0d76321c5191/cr201484f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95fa/4123296/90dc75cf8624/cr201484f6.jpg

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