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

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  • Natalia L. Kononenko

    (Leibniz-Institut für Molekulare Pharmakologie
    NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin
    CECAD Research Center, University of Cologne)

  • Gala A. Claßen

    (Leibniz-Institut für Molekulare Pharmakologie)

  • Marijn Kuijpers

    (Leibniz-Institut für Molekulare Pharmakologie)

  • Dmytro Puchkov

    (Leibniz-Institut für Molekulare Pharmakologie)

  • Tanja Maritzen

    (Leibniz-Institut für Molekulare Pharmakologie)

  • Aleksandra Tempes

    (Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology)

  • Anna R. Malik

    (Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology)

  • Agnieszka Skalecka

    (Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology)

  • Sujoy Bera

    (CECAD Research Center, University of Cologne)

  • Jacek Jaworski

    (Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology)

  • Volker Haucke

    (Leibniz-Institut für Molekulare Pharmakologie
    NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin
    Freie Universität Berlin, Faculty of Biology, Chemistry and Pharmacy)

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.

Suggested Citation

  • Natalia L. Kononenko & Gala A. Claßen & Marijn Kuijpers & Dmytro Puchkov & Tanja Maritzen & Aleksandra Tempes & Anna R. Malik & Agnieszka Skalecka & Sujoy Bera & Jacek Jaworski & Volker Haucke, 2017. "Retrograde transport of TrkB-containing autophagosomes via the adaptor AP-2 mediates neuronal complexity and prevents neurodegeneration," Nature Communications, Nature, vol. 8(1), pages 1-16, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14819
    DOI: 10.1038/ncomms14819
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