Reference - Detail
| RRC ID | 27887 |
|---|---|
| Author | Ma B, Cao W, Li W, Gao C, Qi Z, Zhao Y, Du J, Xue H, Peng J, Wen J, Chen H, Ning Y, Huang L, Zhang H, Gao X, Yu L, Chen YG. |
| Title | Dapper1 promotes autophagy by enhancing the Beclin1-Vps34-Atg14L complex formation. |
| Journal | Cell Res |
| 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. |
| Volume | 24(8) |
| Pages | 912-24 |
| Published | 2014-8-1 |
| DOI | 10.1038/cr.2014.84 |
| PII | cr201484 |
| PMID | 24980960 |
| PMC | PMC4123296 |
| MeSH | Adaptor Proteins, Signal Transducing / deficiency Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism* Adaptor Proteins, Vesicular Transport / metabolism* Animals Apoptosis Regulatory Proteins / metabolism* Autophagy* Autophagy-Related Proteins Beclin-1 Carrier Proteins / metabolism Cell Line Central Nervous System / metabolism Class III Phosphatidylinositol 3-Kinases / metabolism* HEK293 Cells Humans Membrane Proteins / metabolism* Mice Mice, Inbred C57BL Mice, Knockout Microtubule-Associated Proteins / metabolism Nuclear Proteins / deficiency Nuclear Proteins / genetics Nuclear Proteins / metabolism* RNA-Binding Proteins / genetics RNA-Binding Proteins / metabolism Ubiquitination |
| IF | 20.507 |
| Times Cited | 31 |
| WOS Category | CELL BIOLOGY |
| Resource | |
| Mice | RBRC00806 |