Caveolae and Bin1 form ring-shaped platforms for T-tubule initiation
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.
All datasets supporting the findings of this study are available in Dryad
Data from: Caveolae and Bin1 form ring-shaped platforms for T-tubule initiationDryad Digital Repository, doi:10.5061/dryad.k98sf7m98.
Article and author information
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.
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.
- Benjamin L Prosser, University of Pennsylvania Perelman School of Medicine, United States
- Received: October 12, 2022
- Preprint posted: November 3, 2022 (view preprint)
- Accepted: April 20, 2023
- Accepted Manuscript published: April 21, 2023 (version 1)
© 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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