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Nat Commun. 2017 Apr 7;8:14819. doi: 10.1038/ncomms14819.

Retrograde transport of TrkB-containing autophagosomes via the adaptor AP-2 mediates neuronal complexity and prevents neurodegeneration.

Author information

1
Leibniz-Institut für Molekulare Pharmakologie, 13125 Berlin, Germany.
2
NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.
3
CECAD Research Center, University of Cologne, 50931 Cologne, Germany.
4
Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
5
Freie Universität Berlin, Faculty of Biology, Chemistry and Pharmacy, 14195 Berlin, Germany.

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.

PMID:
28387218
PMCID:
PMC5385568
DOI:
10.1038/ncomms14819
[Indexed for MEDLINE]
Free PMC Article

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