The membrane periodic skeleton is an actomyosin network that regulates axonal diameter and conduction

  1. Ana Rita Costa
  2. Sara C Sousa
  3. Rita Pinto-Costa
  4. José C Mateus
  5. Cátia DF Lopes
  6. Ana Catarina Costa
  7. David Rosa
  8. Diana Machado
  9. Luis Pajuelo
  10. Xuewei Wang
  11. Fengquan Zhou
  12. António J Pereira
  13. Paula Sampaio
  14. Boris Y Rubinstein
  15. Inês Mendes Pinto
  16. Marko Lampe
  17. Paulo Aguiar
  18. Monica M Sousa  Is a corresponding author
  1. IBMC/i3S- University of Porto, Portugal
  2. i3S- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
  3. INEB/i3S- University of Porto, Portugal
  4. Johns Hopkins University School of Medicine, United States
  5. i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
  6. Stowers Institute for Medical Research, United States
  7. International Iberian Nanotechnology Laboratory, Portugal
  8. EMBL, Germany
  9. University of Porto, Portugal

Abstract

Neurons have a membrane periodic skeleton (MPS) composed of actin rings interconnected by spectrin. Here, combining chemical and genetic gain- and loss-of-function assays, we show that in rat hippocampal neurons the MPS is an actomyosin network that controls axonal expansion and contraction. Using super-resolution microscopy, we analyzed the localization of axonal non-muscle myosin II (NMII). We show that active NMII light chains are colocalized with actin rings and organized in a circular periodic manner throughout the axon shaft. In contrast, NMII heavy chains are mostly positioned along the longitudinal axonal axis, being able to crosslink adjacent rings. NMII filaments can play contractile or scaffolding roles determined by their position relative to actin rings and activation state. We also show that MPS destabilization through NMII inactivation affects axonal electrophysiology, increasing action potential conduction velocity. In summary, our findings open new perspectives on axon diameter regulation, with important implications in neuronal biology.

Data availability

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

Article and author information

Author details

  1. Ana Rita Costa

    Nerve Regeneration group, IBMC/i3S- University of Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  2. Sara C Sousa

    Nerve Regeneration group, IBMC/i3S- University of Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  3. Rita Pinto-Costa

    Nerve Regeneration group, IBMC/i3S- University of Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  4. José C Mateus

    i3S- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8058-5093
  5. Cátia DF Lopes

    Neuroengineering and Computational Neuroscience group, INEB/i3S- University of Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  6. Ana Catarina Costa

    Nerve Regeneration group, IBMC/i3S- University of Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  7. David Rosa

    Nerve Regeneration group, IBMC/i3S- University of Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  8. Diana Machado

    Nerve Regeneration group, IBMC/i3S- University of Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  9. Luis Pajuelo

    Nerve Regeneration group, IBMC/i3S- University of Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  10. Xuewei Wang

    Orthopaedic Surgery and The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1375-7358
  11. Fengquan Zhou

    Orthopaedic Surgery and The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. António J Pereira

    i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  13. Paula Sampaio

    Advanced Light Microscopy, IBMC/i3S- University of Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  14. Boris Y Rubinstein

    Research Advisory, Stowers Institute for Medical Research, Kansas, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Inês Mendes Pinto

    Nanomedicine, International Iberian Nanotechnology Laboratory, Braga, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  16. Marko Lampe

    Advanced Light Microscopy Facility, EMBL, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4510-9048
  17. Paulo Aguiar

    INEB - Inst Nac Eng Biomedica, University of Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4164-5713
  18. Monica M Sousa

    Nerve Regeneration group, IBMC/i3S- University of Porto, Porto, Portugal
    For correspondence
    msousa@ibmc.up.pt
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4524-2260

Funding

Fundação para a Ciência e a Tecnologia (NORTE-01-0145-FEDER-028623; PTDC/MED-NEU/28623/2017)

  • Monica M Sousa

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

Ethics

Animal experimentation: Experiments were carried out in accordance with the European Union Directive 2010/63/EU and national Decreto-lei nº113-2013. The protocols described were approved by the IBMC Ethical Committee and by the Portuguese Veterinarian Board.

Reviewing Editor

  1. Pekka Lappalainen, University of Helsinki, Finland

Version history

  1. Received: January 24, 2020
  2. Accepted: March 19, 2020
  3. Accepted Manuscript published: March 20, 2020 (version 1)
  4. Version of Record published: March 30, 2020 (version 2)

Copyright

© 2020, Costa 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. Ana Rita Costa
  2. Sara C Sousa
  3. Rita Pinto-Costa
  4. José C Mateus
  5. Cátia DF Lopes
  6. Ana Catarina Costa
  7. David Rosa
  8. Diana Machado
  9. Luis Pajuelo
  10. Xuewei Wang
  11. Fengquan Zhou
  12. António J Pereira
  13. Paula Sampaio
  14. Boris Y Rubinstein
  15. Inês Mendes Pinto
  16. Marko Lampe
  17. Paulo Aguiar
  18. Monica M Sousa
(2020)
The membrane periodic skeleton is an actomyosin network that regulates axonal diameter and conduction
eLife 9:e55471.
https://doi.org/10.7554/eLife.55471

Share this article

https://doi.org/10.7554/eLife.55471

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