PKCθ signaling is required for myoblast fusion by regulating the expression of caveolin-3 and β1D integrin upstream focal adhesion kinase
| العنوان: | PKCθ signaling is required for myoblast fusion by regulating the expression of caveolin-3 and β1D integrin upstream focal adhesion kinase |
|---|---|
| المؤلفون: | Mario Molinaro, Piera Fiore, Valeria Marrocco, Paola Aulino, Piera Smeriglio, Sergio Adamo, Luca Madaro, Marina Bouché |
| المصدر: | Molecular Biology of the Cell |
| بيانات النشر: | American Society for Cell Biology (ASCB), 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Male, Integrin beta Chains, Caveolin 3, Cellular differentiation, Cell Culture Techniques, Cell Communication, Biology, Muscle Development, Cell Fusion, Myoblasts, Gene Knockout Techniques, Mice, Myoblast fusion, medicine, Animals, Regeneration, Myocyte, Phosphorylation, Cell adhesion, Molecular Biology, Cells, Cultured, Myogenin, Mice, Knockout, Focal Adhesions, Cell fusion, Myogenesis, Stem Cells, Gene Expression Regulation, Developmental, PAX7 Transcription Factor, Skeletal muscle, Cell Differentiation, Articles, Cell Biology, Molecular biology, Signaling, Cell biology, Protein Kinase C-delta, medicine.anatomical_structure, Focal Adhesion Protein-Tyrosine Kinases, Signal Transduction |
| الوصف: | Using both in vivo and in vitro protein kinase C (PKC) θ mutant models, we found that PKCθ, the PKC isoform predominantly expressed in skeletal muscle, is required for myoblast fusion and myofiber growth, by regulating focal adhesion kinase activity and, in turn, the expression of the pro-fusion genes caveolin-3 and β1D-integrin. Fusion of mononucleated myoblasts to form multinucleated myofibers is an essential phase of skeletal myogenesis, which occurs during muscle development as well as during postnatal life for muscle growth, turnover, and regeneration. Many cell adhesion proteins, including integrins, have been shown to be important for myoblast fusion in vertebrates, and recently focal adhesion kinase (FAK), has been proposed as a key mediator of myoblast fusion. Here we focused on the possible role of PKCθ, the PKC isoform predominantly expressed in skeletal muscle, in myoblast fusion. We found that the expression of PKCθ is strongly up-regulated following freeze injury–induced muscle regeneration, as well as during in vitro differentiation of satellite cells (SCs; the muscle stem cells). Using both PKCθ knockout and muscle-specific PKCθ dominant-negative mutant mouse models, we observed delayed body and muscle fiber growth during the first weeks of postnatal life, when compared with wild-type (WT) mice. We also found that myofiber formation, during muscle regeneration after freeze injury, was markedly impaired in PKCθ mutant mice, as compared with WT. This phenotype was associated with reduced expression of the myogenic differentiation program executor, myogenin, but not with that of the SC marker Pax7. Indeed in vitro differentiation of primary muscle-derived SCs from PKCθ mutants resulted in the formation of thinner myotubes with reduced numbers of myonuclei and reduced fusion rate, when compared with WT cells. These effects were associated to reduced expression of the profusion genes caveolin-3 and β1D integrin and to reduced activation/phosphorylation of their up-stream regulator FAK. Indeed the exogenous expression of a constitutively active mutant form of PKCθ in muscle cells induced FAK phosphorylation. Moreover pharmacologically mediated full inhibition of FAK activity led to similar fusion defects in both WT and PKCθ-null myoblasts. We thus propose that PKCθ signaling regulates myoblast fusion by regulating, at least in part, FAK activity, essential for profusion gene expression. |
| تدمد: | 1939-4586 1059-1524 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::33575dc86f49d548d4e1241b61f83653Test https://doi.org/10.1091/mbc.e10-10-0821Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....33575dc86f49d548d4e1241b61f83653 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19394586 10591524 |
|---|