Phenotypic behavior of C2C12 myoblasts upon expression of the dystrophy-related caveolin-3 P104L and TFT mutants.
Caveolin-3 (Cav-3) is the main scaffolding protein present in myofiber caveolae. We transfected C2C12 myoblasts with dominant negative forms of Cav-3, P104L or DeltaTFT, respectively, which cause the limb-girdle muscular dystrophy 1-C. Both these forms triggered Cav-3 loss during C2C12 cell differentiation. The P104L mutation reduced myofiber formation by impaired AKT signalling, accompanied by dramatic expression of the E3 ubiquitin ligase Atrogin. On the other hand, the DeltaTFT mutation triggered hypertrophic myotubes sustained by prolonged AKT activation, but independent of increased levels of follistatin and interleukin 4 expression. These data suggest that separated mutations within the same dystrophy-related gene may cause muscle degeneration through different mechanisms.
Fanzani
Alessandro
A
Department of Biomedical Sciences and Biotechnology, Unit of Biochemistry, University of Brescia, Viale Europa 11, 25123 Brescia, Italy. fanzani@med.unibs.it
Stoppani
Elena
E
Gualandi
Laura
L
Giuliani
Roberta
R
Galbiati
Ferruccio
F
Rossi
Stefania
S
Fra
Anna
A
Preti
Augusto
A
Marchesini
Sergio
S
D000818:Animals; D051244:Caveolin 3 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D006801:Humans; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
D051244:Caveolin 3; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases