1. Cell Biology
  2. Neuroscience
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Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins

  1. Belgin Yalçın
  2. Lu Zhao
  3. Martin Stofanko
  4. Niamh C O'Sullivan
  5. Zi Han Kang
  6. Annika Roost
  7. Matthew R Thomas
  8. Sophie Zaessinger
  9. Olivier Blard
  10. Alex L Patto
  11. Anood Sohail
  12. Valentina Baena
  13. Mark Terasaki
  14. Cahir J O'Kane  Is a corresponding author
  1. University of Cambridge, United Kingdom
  2. University of Connecticut Health Center, United States
Research Article
  • Cited 33
  • Views 4,445
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Cite this article as: eLife 2017;6:e23882 doi: 10.7554/eLife.23882

Abstract

Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function.

Article and author information

Author details

  1. Belgin Yalçın

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Lu Zhao

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7528-4034
  3. Martin Stofanko

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Niamh C O'Sullivan

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Zi Han Kang

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Annika Roost

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Matthew R Thomas

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Sophie Zaessinger

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Olivier Blard

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Alex L Patto

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Anood Sohail

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Valentina Baena

    Department of Cell Biology, University of Connecticut Health Center, Farmington, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Mark Terasaki

    Department of Cell Biology, University of Connecticut Health Center, Farmington, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Cahir J O'Kane

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    c.okane@gen.cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3488-2078

Funding

Biotechnology and Biological Sciences Research Council (BB/L021706/1)

  • Lu Zhao
  • Cahir J O'Kane

Wellcome (8136)

  • Martin Stofanko
  • Cahir J O'Kane

European Commission (MCSA fellowships 220851,220874,236777,660516)

  • Lu Zhao
  • Niamh C O'Sullivan
  • Sophie Zaessinger
  • Olivier Blard

Yousef Jameel Foundation

  • Belgin Yalçın

Singapore A*STAR Scholarship (BM/RES/07/005)

  • Zi Han Kang

Cambridge Commonwealth, European and International Trust

  • Belgin Yalçın
  • Anood Sohail

Pakistan Higher Education Council Scholarship

  • Anood Sohail

Motor Neurone Disease Association (Studentship 861-792)

  • Alex L Patto

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

Reviewing Editor

  1. Hugo J Bellen, Howard Hughes Medical Institute, Baylor College of Medicine, United States

Publication history

  1. Received: December 5, 2016
  2. Accepted: July 24, 2017
  3. Accepted Manuscript published: July 25, 2017 (version 1)
  4. Version of Record published: August 30, 2017 (version 2)

Copyright

© 2017, Yalçın 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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