論文 - 詳細
| RRC ID | 88204 |
|---|---|
| 著者 | Kononenko NL, Claßen GA, Kuijpers M, Puchkov D, Maritzen T, Tempes A, Malik AR, Skalecka A, Bera S, Jaworski J, Haucke V. |
| タイトル | Retrograde transport of TrkB-containing autophagosomes via the adaptor AP-2 mediates neuronal complexity and prevents neurodegeneration. |
| ジャーナル | Nat Commun |
| Abstract |
Autophagosomes primarily mediate turnover of cytoplasmic proteins or organelles to provide nutrients and eliminate damaged proteins. In neurons, autophagosomes form in distal axons and are trafficked retrogradely to fuse with lysosomes in the soma. Although defective neuronal autophagy is associated with neurodegeneration, the function of neuronal autophagosomes remains incompletely understood. We show that in neurons, autophagosomes promote neuronal complexity and prevent neurodegeneration in vivo via retrograde transport of brain-derived neurotrophic factor (BDNF)-activated TrkB receptors. p150Glued/dynactin-dependent transport of TrkB-containing autophagosomes requires their association with the endocytic adaptor AP-2, an essential protein complex previously thought to function exclusively in clathrin-mediated endocytosis. These data highlight a novel non-canonical function of AP-2 in retrograde transport of BDNF/TrkB-containing autophagosomes in neurons and reveal a causative link between autophagy and BDNF/TrkB signalling. |
| 巻・号 | 8 |
| ページ | 14819 |
| 公開日 | 2017-4-7 |
| DOI | 10.1038/ncomms14819 |
| PII | ncomms14819 |
| PMID | 28387218 |
| PMC | PMC5385568 |
| MeSH | Adaptor Protein Complex 2 / metabolism* Animals Autophagosomes Autophagy Biological Transport Brain / metabolism Brain / pathology* Brain-Derived Neurotrophic Factor / metabolism Dynactin Complex / metabolism Endocytosis Mice Mice, Knockout Microtubule-Associated Proteins / metabolism Neurons / metabolism Protein Binding Rats, Wistar Receptor, trkB / metabolism* Signal Transduction |
| IF | 12.121 |
| リソース情報 | |
| 実験動物マウス | RBRC02975 |