IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_s41467-017-00689-z.html
   My bibliography  Save this article

Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease

Author

Listed:
  • Patrick Lüningschrör

    (University Hospital Würzburg
    University of Bielefeld)

  • Beyenech Binotti

    (Max Planck Institute for Biophysical Chemistry)

  • Benjamin Dombert

    (University Hospital Würzburg)

  • Peter Heimann

    (University of Bielefeld)

  • Angel Perez-Lara

    (Max Planck Institute for Biophysical Chemistry)

  • Carsten Slotta

    (University of Bielefeld)

  • Nadine Thau-Habermann

    (Hannover Medical School)

  • Cora R. von Collenberg

    (University Hospital Würzburg)

  • Franziska Karl

    (University Hospital Würzburg)

  • Markus Damme

    (Christian-Albrechts-Universität zu Kiel)

  • Arie Horowitz

    (Sidney Kimmel Medical College, Thomas Jefferson University)

  • Isabelle Maystadt

    (Centre de Génétique Humaine, Institut de Pathologie et de Génétique)

  • Annette Füchtbauer

    (Aarhus University)

  • Ernst-Martin Füchtbauer

    (Aarhus University)

  • Sibylle Jablonka

    (University Hospital Würzburg)

  • Robert Blum

    (University Hospital Würzburg)

  • Nurcan Üçeyler

    (University Hospital Würzburg)

  • Susanne Petri

    (Hannover Medical School
    Integrated Research and Treatment Center Transplantation (IFB-Tx) Hannover)

  • Barbara Kaltschmidt

    (University of Bielefeld
    University of Bielefeld)

  • Reinhard Jahn

    (Max Planck Institute for Biophysical Chemistry)

  • Christian Kaltschmidt

    (University of Bielefeld)

  • Michael Sendtner

    (University Hospital Würzburg)

Abstract

Autophagy-mediated degradation of synaptic components maintains synaptic homeostasis but also constitutes a mechanism of neurodegeneration. It is unclear how autophagy of synaptic vesicles and components of presynaptic active zones is regulated. Here, we show that Pleckstrin homology containing family member 5 (Plekhg5) modulates autophagy of synaptic vesicles in axon terminals of motoneurons via its function as a guanine exchange factor for Rab26, a small GTPase that specifically directs synaptic vesicles to preautophagosomal structures. Plekhg5 gene inactivation in mice results in a late-onset motoneuron disease, characterized by degeneration of axon terminals. Plekhg5-depleted cultured motoneurons show defective axon growth and impaired autophagy of synaptic vesicles, which can be rescued by constitutively active Rab26. These findings define a mechanism for regulating autophagy in neurons that specifically targets synaptic vesicles. Disruption of this mechanism may contribute to the pathophysiology of several forms of motoneuron disease.

Suggested Citation

  • Patrick Lüningschrör & Beyenech Binotti & Benjamin Dombert & Peter Heimann & Angel Perez-Lara & Carsten Slotta & Nadine Thau-Habermann & Cora R. von Collenberg & Franziska Karl & Markus Damme & Arie H, 2017. "Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00689-z
    DOI: 10.1038/s41467-017-00689-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-00689-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-017-00689-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Amy-Jayne Hutchings & Bita Hambrecht & Alexander Veh & Neha Jadhav Giridhar & Abdolhossein Zare & Christina Angerer & Thorben Ohnesorge & Maren Schenke & Bhuvaneish T. Selvaraj & Siddharthan Chandran , 2024. "Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Emmanouela Kallergi & Akrivi-Dimitra Daskalaki & Angeliki Kolaxi & Come Camus & Evangelia Ioannou & Valentina Mercaldo & Per Haberkant & Frank Stein & Kyriaki Sidiropoulou & Yannis Dalezios & Mikhail , 2022. "Dendritic autophagy degrades postsynaptic proteins and is required for long-term synaptic depression in mice," Nature Communications, Nature, vol. 13(1), pages 1-23, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00689-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.