title: Retrograde transport of TrkB-containing autophagosomes via the adaptor AP-2 mediates neuronal complexity and prevents neurodegeneration.
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.
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie, 13125 Berlin, Germany.|NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.|CECAD Research Center, University of Cologne, 50931 Cologne, Germany.
authors.forename: Natalia L
authors.initials: NL
authors.lastname: Kononenko
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie, 13125 Berlin, Germany.
authors.forename: Gala A
authors.initials: GA
authors.lastname: Claßen
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie, 13125 Berlin, Germany.
authors.forename: Marijn
authors.initials: M
authors.lastname: Kuijpers
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie, 13125 Berlin, Germany.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Puchkov
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie, 13125 Berlin, Germany.
authors.forename: Tanja
authors.identifier: 0000-0003-4993-0340
authors.initials: T
authors.lastname: Maritzen
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Tempes
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Malik
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Skalecka
authors.affiliation: CECAD Research Center, University of Cologne, 50931 Cologne, Germany.
authors.forename: Sujoy
authors.initials: S
authors.lastname: Bera
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jaworski
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie, 13125 Berlin, Germany.|NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.|Freie Universität Berlin, Faculty of Biology, Chemistry and Pharmacy, 14195 Berlin, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Haucke
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000378:metabolism*; D000818:Animals; D000071182:Autophagosomes; D001343:Autophagy; D001692:Biological Transport; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D000072159:Dynactin Complex / Q000378:metabolism; D004705:Endocytosis; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D033962:Adaptor Protein Complex 2; D019208:Brain-Derived Neurotrophic Factor; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D020813:Receptor, trkB; C000606364:Dctn1 protein, mouse; C526109:Anxa3 protein, rat