The GTPase Rab26 links synaptic vesicles to the autophagy pathway

  1. Beyenech Binotti
  2. Nathan J Pavlos
  3. Dietmar Riedel
  4. Dirk Wenzel
  5. Gerd VorbrĂĽggen
  6. Amanda M Schalk
  7. Karin KĂĽhnel
  8. Janina Boyken
  9. Christian Erck
  10. Henrik Martens
  11. John J E Chua
  12. Reinhard Jahn  Is a corresponding author
  1. Max Planck Institute for Biophysical Chemistry, Germany
  2. University of Western Australia, Australia
  3. University of Illinois at Chicago, United States
  4. Bayer Pharma Aktiengesellschaft, Germany
  5. Synaptic Systems GmbH, Germany

Abstract

Small GTPases of the Rab family not only regulate target recognition in membrane traffic but also control other cellular functions such as cytoskeletal transport and autophagy. Here we show that Rab26 is specifically associated with clusters of synaptic vesicles in neurites. Overexpression of active but not of GDP-preferring Rab26 enhances vesicle clustering, which is particularly conspicuous for the EGFP-tagged variant, resulting in a massive accumulation of synaptic vesicles in neuronal somata without altering the distribution of other organelles. Both endogenous and induced clusters co-localize with autophagy-related proteins such as Atg16L1, LC3B and Rab33B but not with other organelles. Furthermore, Atg16L1 appears to be a direct effector of Rab26 and binds Rab26 in its GTP-bound form, albeit only with low affinity. We propose that Rab26 selectively directs synaptic and secretory vesicles into preautophagosomal structures, suggesting the presence of a novel pathway for degradation of synaptic vesicles.

Article and author information

Author details

  1. Beyenech Binotti

    Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    No competing interests declared.
  2. Nathan J Pavlos

    School Of Surgery, University of Western Australia, Crawley, Australia
    Competing interests
    No competing interests declared.
  3. Dietmar Riedel

    Facility for Transmission Electron Microscopy, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    No competing interests declared.
  4. Dirk Wenzel

    Facility for Transmission Electron Microscopy, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    No competing interests declared.
  5. Gerd VorbrĂĽggen

    Research Group Molecular Cell Dynamics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    No competing interests declared.
  6. Amanda M Schalk

    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Ashland, United States
    Competing interests
    No competing interests declared.
  7. Karin KĂĽhnel

    Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    No competing interests declared.
  8. Janina Boyken

    Gynecological Therapies, Bayer Pharma Aktiengesellschaft, Berlin, Germany
    Competing interests
    No competing interests declared.
  9. Christian Erck

    Synaptic Systems GmbH, Göttingen, Germany
    Competing interests
    No competing interests declared.
  10. Henrik Martens

    Synaptic Systems GmbH, Göttingen, Germany
    Competing interests
    No competing interests declared.
  11. John J E Chua

    Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    No competing interests declared.
  12. Reinhard Jahn

    Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    For correspondence
    rjahn@gwdg.de
    Competing interests
    Reinhard Jahn, Reviewing editor, eLife.

Copyright

© 2015, Binotti 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. Beyenech Binotti
  2. Nathan J Pavlos
  3. Dietmar Riedel
  4. Dirk Wenzel
  5. Gerd VorbrĂĽggen
  6. Amanda M Schalk
  7. Karin KĂĽhnel
  8. Janina Boyken
  9. Christian Erck
  10. Henrik Martens
  11. John J E Chua
  12. Reinhard Jahn
(2015)
The GTPase Rab26 links synaptic vesicles to the autophagy pathway
eLife 4:e05597.
https://doi.org/10.7554/eLife.05597

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https://doi.org/10.7554/eLife.05597

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