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Myoblast mechanotransduction and myotube morphology is dependent on BAG3 regulation of YAP and TAZ.
Günay, K Arda; Silver, Jason S; Chang, Tze-Ling; Bednarski, Olivia J; Bannister, Kendra L; Rogowski, Cameron J; Olwin, Bradley B; Anseth, Kristi S.
Afiliación
  • Günay KA; Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO, USA; BioFrontiers Institute, University of Colorado, Boulder, CO, USA.
  • Silver JS; Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO, USA; BioFrontiers Institute, University of Colorado, Boulder, CO, USA; Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO, USA; Medical Scientist Training Program, Un
  • Chang TL; Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO, USA; BioFrontiers Institute, University of Colorado, Boulder, CO, USA.
  • Bednarski OJ; Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO, USA; BioFrontiers Institute, University of Colorado, Boulder, CO, USA.
  • Bannister KL; Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO, USA; BioFrontiers Institute, University of Colorado, Boulder, CO, USA.
  • Rogowski CJ; Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO, USA; BioFrontiers Institute, University of Colorado, Boulder, CO, USA.
  • Olwin BB; BioFrontiers Institute, University of Colorado, Boulder, CO, USA; Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO, USA. Electronic address: Olwin@colorado.edu.
  • Anseth KS; Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO, USA; BioFrontiers Institute, University of Colorado, Boulder, CO, USA. Electronic address: Kristi.anseth@colorado.edu.
Biomaterials ; 277: 121097, 2021 10.
Article en En | MEDLINE | ID: mdl-34481290
Skeletal muscle tissue is mechanically dynamic with changes in stiffness influencing function, maintenance, and regeneration. We modeled skeletal muscle mechanical changes in culture with dynamically stiffening hydrogels demonstrating that the chaperone protein BAG3 transduces matrix stiffness by redistributing YAP and TAZ subcellular localization in muscle progenitor cells. BAG3 depletion increases cytoplasmic retention of YAP and TAZ, desensitizing myoblasts to changes in hydrogel elastic moduli. Upon differentiation, muscle progenitors depleted of BAG3 formed enlarged, round myotubes lacking the typical cylindrical morphology. The aberrant morphology is dependent on YAP/TAZ signaling, which was sequestered in the cytoplasm in BAG3-depleted myotubes but predominately nuclear in cylindrical myotubes of control cells. Control progenitor cells induced to differentiate on soft (E' = 4 and 12 kPa) hydrogels formed circular myotubes similar to those observed in BAG3-depleted cells. Inhibition of the Hippo pathway partially restored myotube morphologies, permitting nuclear translocation of YAP and TAZ in BAG3-depleted myogenic progenitors. Thus, BAG3 is a critical mediator of dynamic stiffness changes in muscle tissue, coupling mechanical alterations to intracellular signals and inducing changes in gene expression that influence muscle progenitor cell morphology and differentiation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mecanotransducción Celular / Proteínas Adaptadoras Transductoras de Señales Tipo de estudio: Prognostic_studies Idioma: En Revista: Biomaterials Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mecanotransducción Celular / Proteínas Adaptadoras Transductoras de Señales Tipo de estudio: Prognostic_studies Idioma: En Revista: Biomaterials Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos