title: Point mutated caveolin-3 form (P104L) impairs myoblast differentiation via Akt and p38 signalling reduction, leading to an immature cell signature.
abstract: Unbalanced levels of caveolin-3 (Cav3) are involved in muscular disorders. In the present study we show that differentiation of immortalized myoblasts is affected by either lack or overexpression of Cav3. Nevertheless, depletion of Cav3 induced by delivery of the dominant-negative Cav3 (P104L) form elicited a more severe phenotype, characterized by the simultaneous attenuation of the Akt and p38 signalling networks, leading to an immature cell and molecular signature. Accordingly, differentiation of myoblasts harbouring Cav3 (P104L) was improved by countering the reduced Akt and p38 signalling network via administration of IGF-1 or trichostatin A. Furthermore, loss of Cav3 correlated with a deregulation of the TGF-β-induced Smad2 and Erk1/2 pathways, confirming that Cav3 controls TGF-β signalling at the plasma membrane. Overall, these data suggest that loss of Cav3, primarily causing attenuation of both Akt and p38 pathways, contributes to impair myoblast fusion.
authors.affiliation: Department of Biomedical Sciences and Biotechnologies and Interuniversity Institute of Myology (IIM), University of Brescia, Brescia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Stoppani
authors.forename: Stefania
authors.initials: S
authors.lastname: Rossi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Meacci
authors.forename: Fabio
authors.initials: F
authors.lastname: Penna
authors.forename: Paola
authors.initials: P
authors.lastname: Costelli
authors.forename: Arianna
authors.initials: A
authors.lastname: Bellucci
authors.forename: Fiorella
authors.initials: F
authors.lastname: Faggi
authors.forename: Daniele
authors.initials: D
authors.lastname: Maiolo
authors.forename: Eugenio
authors.initials: E
authors.lastname: Monti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fanzani
mesh_terms: D000818:Animals; D051244:Caveolin 3 / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002459:Cell Fusion; D002460:Cell Line; D005786:Gene Expression Regulation; D006877:Hydroxamic Acids / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D017354:Point Mutation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D051244:Caveolin 3; D006877:Hydroxamic Acids; D011500:Protein Synthesis Inhibitors; D016212:Transforming Growth Factor beta; C012589:trichostatin A; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases