| | Phenotypic behavior of C2C12 myoblasts upon expression of the dystrophy-related caveolin-3 P104L and TFT mutantsEdited by Horst Feldmann Received 25 June 2007; received in revised form 19 September 2007; accepted 26 September 2007. published online 04 October 2007. Abstract 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 ΔTFT, 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 ΔTFT 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. Abbreviations: DMEM, Dulbecco’s modified Eagle’s medium, FBS, fetal bovine serum, HS, horse serum, MHC, myosin heavy chain, NFATC, nuclear factor of activated T-cells, IL-4, Interleukin 4 a Department of Biomedical Sciences and Biotechnology, Unit of Biochemistry, University of Brescia, Viale Europa 11, 25123 Brescia, Italy b Department of Biomedical Sciences and Biotechnology, Unit of General Pathology, University of Brescia, Italy c Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh PA, USA d Department of Biomedical Sciences and Biotechnology, Unit of Pathology and Immunology, University of Brescia, Italy  Corresponding author. Fax: +39 030 3701157.
PII: S0014-5793(07)01039-3 doi:10.1016/j.febslet.2007.09.055 © 2007 Federation of European Biochemical Societies | |
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ABSTRACT
