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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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Dewulf, Melissa, Köster, Darius, Sinha, Bidisha, Viaris de Lesegno, Christine, Chambon, Valérie, Bigot, Anne, Bensalah, Mona, Negroni, Elisa, Tardif, Nicolas, Podkalicka, Joanna, Johannes, Ludger, Nassoy, Pierre, Butler-Browne, Gillian, Lamaze, Christophe and Blouin, Cedric M. (2019) Dystrophy-associated caveolin-3 mutations reveal that caveolae couple IL6/STAT3 signaling with mechanosensing in human muscle cells. Nature Communications, 10 (1). 1974 . doi:10.1038/s41467-019-09405-5 ISSN 2041-1723.
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WRAP-dystrophy-associated-mutations-reveal-caveolae-signaling-cells-Koster-2019.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (4042Kb) | Preview |
Official URL: http://dx.doi.org/10.1038/s41467-019-09405-5
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 CAV3P28L 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 ofcaveolin-3. Our study reveals that under mechanical stress the regulation of mechan-oprotection by caveolae is directly coupled with the regulation of IL6/STAT3 signaling inmuscle cells and that this regulation is absent in Cav3-associated dystrophic patients.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||
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Subjects: | Q Science > QP Physiology R Medicine > RB Pathology |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Dystrophy -- Physiological aspects, Muscle proteins, Genetics | ||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Nature Communications | ||||||||||||||||||||||||||||||||||||
Publisher: | Nature Publishing Group | ||||||||||||||||||||||||||||||||||||
ISSN: | 2041-1723 | ||||||||||||||||||||||||||||||||||||
Official Date: | 29 April 2019 | ||||||||||||||||||||||||||||||||||||
Dates: |
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Volume: | 10 | ||||||||||||||||||||||||||||||||||||
Number: | 1 | ||||||||||||||||||||||||||||||||||||
Article Number: | 1974 | ||||||||||||||||||||||||||||||||||||
DOI: | 10.1038/s41467-019-09405-5 | ||||||||||||||||||||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||||||||||||||
Date of first compliant deposit: | 29 April 2019 | ||||||||||||||||||||||||||||||||||||
Date of first compliant Open Access: | 30 April 2019 | ||||||||||||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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