Caveolae and Bin1 form ring-shaped platforms for T-tubule initiation

  1. Eline Lemerle
  2. Jeanne Lainé
  3. Marion Benoist
  4. Gilles Moulay
  5. Anne Bigot
  6. Clémence Labasse
  7. Angéline Madelaine
  8. Alexis Canette
  9. Perrine Aubin
  10. Jean-Michel Vallat
  11. Norma B Romero
  12. Marc Bitoun
  13. Vincent Mouly
  14. Isabelle Marty
  15. Bruno Cadot
  16. Laura Picas
  17. Stéphane Vassilopoulos  Is a corresponding author
  1. Sorbonne Université, INSERM, France
  2. Pitié-Salpêtrière Hospital, France
  3. Sorbonne Université, France
  4. University Grenoble Alpes, INSERM, France
  5. University Hospital, France
  6. CNRS UMR 9004, Université de Montpellier, France

Abstract

Excitation-contraction coupling requires a highly specialized membrane structure, the triad, composed of a plasma membrane invagination, the T-tubule, surrounded by two sarcoplasmic reticulum terminal cisternae. Although the precise mechanisms governing T-tubule biogenesis and triad formation remain largely unknown, studies have shown that caveolae participate in T-tubule formation and mutations of several of their constituents induce muscle weakness and myopathies. Here, we demonstrate that, at the plasma membrane, Bin1 and caveolae composed of caveolin-3 assemble into ring-like structures from which emerge tubes enriched in the dihydropyridine receptor. Bin1 expression lead to the formation of both rings and tubes and we show that Bin1 forms scaffolds on which caveolae accumulate to form the initial T-tubule. Cav3 deficiency caused by either gene silencing or pathogenic mutations results in defective ring formation and perturbed Bin1-mediated tubulation that may explain defective T-tubule organization in mature muscles. Our results uncover new pathophysiological mechanisms that may prove relevant to myopathies caused by Cav3 or Bin1 dysfunction.

Data availability

All datasets supporting the findings of this study are available in Dryad

The following data sets were generated

Article and author information

Author details

  1. Eline Lemerle

    Institut de Myologie, Sorbonne Université, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Jeanne Lainé

    Institut de Myologie, Sorbonne Université, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Marion Benoist

    Institut de Myologie, Sorbonne Université, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Gilles Moulay

    Institut de Myologie, Sorbonne Université, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Anne Bigot

    Institut de Myologie, Sorbonne Université, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Clémence Labasse

    Neuromuscular Morphology Unit, Pitié-Salpêtrière Hospital, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Angéline Madelaine

    Neuromuscular Morphology Unit, Pitié-Salpêtrière Hospital, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Alexis Canette

    Institut de Biologie Paris-Seine, Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2750-6568
  9. Perrine Aubin

    Grenoble Institut des Neurosciences, University Grenoble Alpes, INSERM, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Jean-Michel Vallat

    Department of Neurology, University Hospital, Limoges, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Norma B Romero

    Neuromuscular Morphology Unit, Pitié-Salpêtrière Hospital, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  12. Marc Bitoun

    Institut de Myologie, Sorbonne Université, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  13. Vincent Mouly

    Institut de Myologie, Sorbonne Université, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  14. Isabelle Marty

    Grenoble Institut des Neurosciences, University Grenoble Alpes, INSERM, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  15. Bruno Cadot

    Institut de Myologie, Sorbonne Université, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  16. Laura Picas

    Institut de Recherche en Infectiologie de Montpellier (IRIM), CNRS UMR 9004, Université de Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5619-5228
  17. Stéphane Vassilopoulos

    Institut de Myologie, Sorbonne Université, INSERM, Paris, France
    For correspondence
    s.vassilopoulos@institut-myologie.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0172-330X

Funding

Agence Nationale de la Recherche (ANR-21-CE13-0018-01)

  • Stéphane Vassilopoulos

Agence Nationale de la Recherche (ANR-18-CE17-0006-02)

  • Marc Bitoun

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

Reviewing Editor

  1. Benjamin L Prosser, University of Pennsylvania Perelman School of Medicine, United States

Ethics

Animal experimentation: Animal studies conform to the French laws and regulations concerning the use of animals for research and were approved by an external ethics committee (approval no. 00351.02 delivered by the French Ministry of Higher Education and Scientific Research).

Human subjects: For human studies, all individuals provided informed consent for muscle biopsies according to a protocol approved by the ethics committee of the Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Assistance Publique-Hôpitaux de Paris, GH Pitié-Salpêtrière, Paris, France.

Version history

  1. Received: October 12, 2022
  2. Preprint posted: November 3, 2022 (view preprint)
  3. Accepted: April 20, 2023
  4. Accepted Manuscript published: April 21, 2023 (version 1)
  5. Version of Record published: June 20, 2023 (version 2)

Copyright

© 2023, Lemerle 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. Eline Lemerle
  2. Jeanne Lainé
  3. Marion Benoist
  4. Gilles Moulay
  5. Anne Bigot
  6. Clémence Labasse
  7. Angéline Madelaine
  8. Alexis Canette
  9. Perrine Aubin
  10. Jean-Michel Vallat
  11. Norma B Romero
  12. Marc Bitoun
  13. Vincent Mouly
  14. Isabelle Marty
  15. Bruno Cadot
  16. Laura Picas
  17. Stéphane Vassilopoulos
(2023)
Caveolae and Bin1 form ring-shaped platforms for T-tubule initiation
eLife 12:e84139.
https://doi.org/10.7554/eLife.84139

Share this article

https://doi.org/10.7554/eLife.84139

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