Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice

  1. Sheila Hoffmann-Conaway
  2. Marisa M Brockmann
  3. Katharina Schneider
  4. Anil Annamneedi
  5. Kazi Atikur Rahman
  6. Christine Bruns
  7. Kathrin Textoris-Taube
  8. Thorsten Trimbuch
  9. Karl-Heinz Smalla
  10. Christian Rosenmund
  11. Eckart D Gundelfinger
  12. Craig Curtis Garner  Is a corresponding author
  13. Carolina Montenegro-Venegas  Is a corresponding author
  1. German Center for Neurodegenerative Diseases, Germany
  2. Charité - Universitätsmedizin Berlin, Germany
  3. Leibniz Institute for Neurobiology, Germany

Abstract

Mechanisms regulating the turnover of synaptic vesicle (SV) proteins are not well understood. They are thought to require poly-ubiquitination and degradation through proteasome, endo-lysosomal or autophagy-related pathways. Bassoon was shown to negatively regulate presynaptic autophagy in part by scaffolding Atg5. Here, we show that increased autophagy in Bassoon knockout neurons depends on poly-ubiquitination and that the loss of Bassoon leads to elevated levels of ubiquitinated synaptic proteins per se. Our data show that Bassoon knockout neurons have a smaller SV pool size and a higher turnover rate as indicated by a younger pool of SV2. The E3 ligase Parkin is required for increased autophagy in Bassoon-deficient neurons as the knockdown of Parkin normalized autophagy and SV protein levels and rescued impaired SV recycling. These data indicate that Bassoon is a key regulator of SV proteostasis and that Parkin is a key E3 ligase in the autophagy-mediated clearance of SV proteins.

Data availability

All data generated or analysed during this study are included in the manuscript.

Article and author information

Author details

  1. Sheila Hoffmann-Conaway

    German Center for Neurodegenerative Diseases, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Marisa M Brockmann

    Institut für Neurophysiologie, Charité - Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1386-5359
  3. Katharina Schneider

    German Center for Neurodegenerative Diseases, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Anil Annamneedi

    Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Kazi Atikur Rahman

    German Center for Neurodegenerative Diseases, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8124-6026
  6. Christine Bruns

    German Center for Neurodegenerative Diseases, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Kathrin Textoris-Taube

    Institute of Biochemistry, Core Facility High Throughput Mass Spectrometry, Charité - Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Thorsten Trimbuch

    Department of Neurophysiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Karl-Heinz Smalla

    Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Christian Rosenmund

    Institut für Neurophysiologie, Charité - Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3905-2444
  11. Eckart D Gundelfinger

    Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  12. Craig Curtis Garner

    German Center for Neurodegenerative Diseases, Berlin, Germany
    For correspondence
    craig.garner@dzne.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1970-5417
  13. Carolina Montenegro-Venegas

    Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany
    For correspondence
    cmontene@lin-magdeburg.de
    Competing interests
    The authors declare that no competing interests exist.

Funding

Federal Government of Germany (SFB958)

  • Craig Curtis Garner

Federal Government of Germany (SFB779/B09)

  • Eckart D Gundelfinger

BMBF (20150065)

  • Eckart D Gundelfinger

BMBF (20150065)

  • Karl-Heinz Smalla

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Breeding of animals and experiments using animal material were carried out in accordance with the European Communities Council Directive (2010/63/EU) and approved by the local animal care committees of Sachsen-Anhalt or the animal welfare committee of Charité Medical University and the Berlin state government (protocol number: T0036/14, O0208/16).

Reviewing Editor

  1. Eunjoon Kim, Institute for Basic Science, Korea Advanced Institute of Science and Technology, Republic of Korea

Publication history

  1. Received: March 3, 2020
  2. Accepted: May 2, 2020
  3. Accepted Manuscript published: May 4, 2020 (version 1)
  4. Version of Record published: May 14, 2020 (version 2)

Copyright

© 2020, Hoffmann-Conaway et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Sheila Hoffmann-Conaway
  2. Marisa M Brockmann
  3. Katharina Schneider
  4. Anil Annamneedi
  5. Kazi Atikur Rahman
  6. Christine Bruns
  7. Kathrin Textoris-Taube
  8. Thorsten Trimbuch
  9. Karl-Heinz Smalla
  10. Christian Rosenmund
  11. Eckart D Gundelfinger
  12. Craig Curtis Garner
  13. Carolina Montenegro-Venegas
(2020)
Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice
eLife 9:e56590.
https://doi.org/10.7554/eLife.56590

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