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

Autor: Dewulf M; Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie - Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143, Paris, 75248, France., Köster DV; Centre for Mechanochemical Cell Biology and Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK., Sinha B; Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur, 741 246, West Bengal, India., Viaris de Lesegno C; Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie - Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143, Paris, 75248, France., Chambon V; Endocytic Trafficking and Intracellular Delivery Laboratory, Institut Curie - Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143, Paris, 75248, France., Bigot A; Association Institut de Myologie, Centre de Recherche en Myologie, Sorbonne Université, INSERM, UMRS974, Paris, 75013, France., Bensalah M; Association Institut de Myologie, Centre de Recherche en Myologie, Sorbonne Université, INSERM, UMRS974, Paris, 75013, France., Negroni E; Association Institut de Myologie, Centre de Recherche en Myologie, Sorbonne Université, INSERM, UMRS974, Paris, 75013, France., Tardif N; Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie - Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143, Paris, 75248, France., Podkalicka J; Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie - Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143, Paris, 75248, France.; Laboratoire Physico-Chimie Curie, Institut Curie, PSL Research University, CNRS UMR168, Sorbonne Université, Paris, 75231, France.; Laboratory of Cytobiochemistry, Faculty of Biotechnology, University of Wrocław, Wrocław, 50-383, Poland., Johannes L; Endocytic Trafficking and Intracellular Delivery Laboratory, Institut Curie - Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143, Paris, 75248, France., Nassoy P; LP2N, CNRS UMR 5298, IOA, Institut d'Optique Graduate School, Université de Bordeaux, Talence, 33400, France., Butler-Browne G; Association Institut de Myologie, Centre de Recherche en Myologie, Sorbonne Université, INSERM, UMRS974, Paris, 75013, France., Lamaze C; Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie - Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143, Paris, 75248, France. christophe.lamaze@curie.fr., Blouin CM; Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie - Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143, Paris, 75248, France. cedric.blouin@curie.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2019 Apr 29; Vol. 10 (1), pp. 1974. Date of Electronic Publication: 2019 Apr 29.
DOI: 10.1038/s41467-019-09405-5
Abstrakt: 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.
Databáze: MEDLINE
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