Dynamic early clusters of nodal proteins contribute to node of Ranvier assembly during myelination of peripheral neurons

  1. Elise LV Malavasi
  2. Aniket Ghosh
  3. Daniel G Booth
  4. Michele Zagnoni
  5. Diane L Sherman
  6. Peter J Brophy  Is a corresponding author
  1. University of Edinburgh, United Kingdom
  2. University of Nottingham, United Kingdom
  3. University of Strathclyde, United Kingdom

Abstract

Voltage-gated sodium channels cluster in macromolecular complexes at nodes of Ranvier to promote rapid nerve impulse conduction in vertebrate nerves. Node assembly in peripheral nerves is thought to be initiated at heminodes at the extremities of myelinating Schwann cells and fusion of heminodes results in the establishment of nodes. Here we show that assembly of 'early clusters' of nodal proteins in the murine axonal membrane precedes heminode formation. The Neurofascin (Nfasc) proteins are essential for node assembly, and the formation of early clusters also requires neuronal Nfasc. Early clusters are mobile and their proteins are dynamically recruited by lateral diffusion. They can undergo fusion not only with each other but also with heminodes thus contributing to the development of nodes in peripheral axons. The formation of early clusters constitutes the earliest stage in peripheral node assembly and expands the repertoire of strategies that have evolved to establish these essential structures.

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Author details

  1. Elise LV Malavasi

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2240-0553
  2. Aniket Ghosh

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3771-6390
  3. Daniel G Booth

    Biodiscovery Institute, University of Nottingham, Nottingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Michele Zagnoni

    Centre for Microsystems and Photonics, Electronic and Electrical Engineering, University of Strathclyde, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Diane L Sherman

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3104-6656
  6. Peter J Brophy

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    peter.brophy@ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0262-9545

Funding

Wellcome Trust (107008)

  • Peter J Brophy

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

Ethics

Animal experimentation: All animal work conformed to UK legislation (Scientific Procedures) Act 1986 and to the University of Edinburgh Ethical Review policy and was performed under Project Licence No. P0F4A25E9 from the Animals in Science Regulation Unit of the UK Home Office.

Reviewing Editor

  1. Moses V Chao, New York University Langone Medical Center, United States

Publication history

  1. Received: March 4, 2021
  2. Accepted: July 7, 2021
  3. Accepted Manuscript published: July 9, 2021 (version 1)
  4. Version of Record published: July 19, 2021 (version 2)

Copyright

© 2021, Malavasi 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. Elise LV Malavasi
  2. Aniket Ghosh
  3. Daniel G Booth
  4. Michele Zagnoni
  5. Diane L Sherman
  6. Peter J Brophy
(2021)
Dynamic early clusters of nodal proteins contribute to node of Ranvier assembly during myelination of peripheral neurons
eLife 10:e68089.
https://doi.org/10.7554/eLife.68089

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