PMID- 28387218 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20181211 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 8 DP - 2017 Apr 7 TI - Retrograde transport of TrkB-containing autophagosomes via the adaptor AP-2 mediates neuronal complexity and prevents neurodegeneration. PG - 14819 LID - 10.1038/ncomms14819 [doi] LID - 14819 AB - 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. p150(Glued)/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. FAU - Kononenko, Natalia L AU - Kononenko NL AD - Leibniz-Institut fur Molekulare Pharmakologie, 13125 Berlin, Germany. AD - NeuroCure Cluster of Excellence, Charite Universitatsmedizin Berlin, 10117 Berlin, Germany. AD - CECAD Research Center, University of Cologne, 50931 Cologne, Germany. FAU - Classen, Gala A AU - Classen GA AD - Leibniz-Institut fur Molekulare Pharmakologie, 13125 Berlin, Germany. FAU - Kuijpers, Marijn AU - Kuijpers M AD - Leibniz-Institut fur Molekulare Pharmakologie, 13125 Berlin, Germany. FAU - Puchkov, Dmytro AU - Puchkov D AD - Leibniz-Institut fur Molekulare Pharmakologie, 13125 Berlin, Germany. FAU - Maritzen, Tanja AU - Maritzen T AUID- ORCID: 0000-0003-4993-0340 AD - Leibniz-Institut fur Molekulare Pharmakologie, 13125 Berlin, Germany. FAU - Tempes, Aleksandra AU - Tempes A AD - Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland. FAU - Malik, Anna R AU - Malik AR AD - Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland. FAU - Skalecka, Agnieszka AU - Skalecka A AD - Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland. FAU - Bera, Sujoy AU - Bera S AD - CECAD Research Center, University of Cologne, 50931 Cologne, Germany. FAU - Jaworski, Jacek AU - Jaworski J AD - Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland. FAU - Haucke, Volker AU - Haucke V AD - Leibniz-Institut fur Molekulare Pharmakologie, 13125 Berlin, Germany. AD - NeuroCure Cluster of Excellence, Charite Universitatsmedizin Berlin, 10117 Berlin, Germany. AD - Freie Universitat Berlin, Faculty of Biology, Chemistry and Pharmacy, 14195 Berlin, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170407 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Adaptor Protein Complex 2) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Dctn1 protein, mouse) RN - 0 (Dynactin Complex) RN - 0 (LC3 protein, rat) RN - 0 (Microtubule-Associated Proteins) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Adaptor Protein Complex 2/*metabolism MH - Animals MH - Autophagosomes MH - Autophagy MH - Biological Transport MH - Brain/metabolism/*pathology MH - Brain-Derived Neurotrophic Factor/metabolism MH - Dynactin Complex/metabolism MH - Endocytosis MH - Mice MH - Mice, Knockout MH - Microtubule-Associated Proteins/metabolism MH - Neurons/metabolism MH - Protein Binding MH - Rats, Wistar MH - Receptor, trkB/*metabolism MH - Signal Transduction PMC - PMC5385568 COIS- The authors declare no competing financial interests. EDAT- 2017/04/08 06:00 MHDA- 2018/12/12 06:00 PMCR- 2017/04/07 CRDT- 2017/04/08 06:00 PHST- 2016/07/27 00:00 [received] PHST- 2017/02/06 00:00 [accepted] PHST- 2017/04/08 06:00 [entrez] PHST- 2017/04/08 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2017/04/07 00:00 [pmc-release] AID - ncomms14819 [pii] AID - 10.1038/ncomms14819 [doi] PST - epublish SO - Nat Commun. 2017 Apr 7;8:14819. doi: 10.1038/ncomms14819.