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Dystrophy-associated caveolin-3 mutations reveal that caveolae couple IL6/STAT3 signaling with mechanosensing in human muscle cells

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  • Melissa Dewulf

    (Institut Curie – Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143)

  • Darius Vasco Köster

    (University of Warwick)

  • Bidisha Sinha

    (Indian Institute of Science Education and Research (IISER) Kolkata)

  • Christine Viaris de Lesegno

    (Institut Curie – Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143)

  • Valérie Chambon

    (Institut Curie – Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143)

  • Anne Bigot

    (Sorbonne Université, INSERM, UMRS974)

  • Mona Bensalah

    (Sorbonne Université, INSERM, UMRS974)

  • Elisa Negroni

    (Sorbonne Université, INSERM, UMRS974)

  • Nicolas Tardif

    (Institut Curie – Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143)

  • Joanna Podkalicka

    (Institut Curie – Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143
    Sorbonne Université
    University of Wrocław)

  • Ludger Johannes

    (Institut Curie – Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143)

  • Pierre Nassoy

    (IOA, Institut d’Optique Graduate School, Université de Bordeaux)

  • Gillian Butler-Browne

    (Sorbonne Université, INSERM, UMRS974)

  • Christophe Lamaze

    (Institut Curie – Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143)

  • Cedric M. Blouin

    (Institut Curie – Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143)

Abstract

Caveolin-3 is the major structural protein of caveolae in muscle. Mutations in the CAV3 gene cause different types of myopathies with altered membrane integrity and repair, expression of muscle proteins, and regulation of signaling pathways. We show here that myotubes from patients bearing the CAV3 P28L and R26Q mutations present a dramatic decrease of caveolae at the plasma membrane, resulting in abnormal response to mechanical stress. Mutant myotubes are unable to buffer the increase in membrane tension induced by mechanical stress. This results in impaired regulation of the IL6/STAT3 signaling pathway leading to its constitutive hyperactivation and increased expression of muscle genes. These defects are fully reversed by reassembling functional caveolae through expression of caveolin-3. Our study reveals that under mechanical stress the regulation of mechanoprotection by caveolae is directly coupled with the regulation of IL6/STAT3 signaling in muscle cells and that this regulation is absent in Cav3-associated dystrophic patients.

Suggested Citation

  • Melissa Dewulf & Darius Vasco Köster & Bidisha Sinha & Christine Viaris de Lesegno & Valérie Chambon & Anne Bigot & Mona Bensalah & Elisa Negroni & Nicolas Tardif & Joanna Podkalicka & Ludger Johannes, 2019. "Dystrophy-associated caveolin-3 mutations reveal that caveolae couple IL6/STAT3 signaling with mechanosensing in human muscle cells," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09405-5
    DOI: 10.1038/s41467-019-09405-5
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    Cited by:

    1. Claudia Matthaeus & Kem A. Sochacki & Andrea M. Dickey & Dmytro Puchkov & Volker Haucke & Martin Lehmann & Justin W. Taraska, 2022. "The molecular organization of differentially curved caveolae indicates bendable structural units at the plasma membrane," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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