title: Remodelling of the nuclear lamina and nucleoskeleton is required for skeletal muscle differentiation in vitro.
abstract: Changes in the expression and distribution of nuclear lamins were investigated during C2C12 myoblast differentiation. The expression of most lamins was unchanged during myogenesis. By contrast, lamin-B2 expression increased and LAP2alpha expression decreased twofold. These changes were correlated with reduced solubility and redistribution of A-type lamins. When C2C12 myoblasts were transfected with a lamin-A mutant that causes autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD), the mutant protein accumulated in the nucleoplasm and exerted dominant influences over endogenous lamins. Myoblasts transfected with wild-type lamins differentiated, albeit more slowly, whereas myoblasts transfected with mutant lamins failed to differentiate. Myoblast differentiation requires dephosphorylation of the retinoblastoma protein Rb. During myogenesis, Rb was rapidly and progressively dephosphorylated. Underphosphorylated Rb formed complexes with LAP2alpha in proliferating myoblasts and postmitotic myoblasts. In myoblasts transfected with the mutant lamins, this complex was disrupted. These data suggest that remodelling of the nucleoskeleton is necessary for skeletal-muscle differentiation and for correct regulation of Rb pathways.
authors.affiliation: Integrative Cell Biology Laboratory, School of Biological and Biomedical Sciences, University of Durham, South Road, Durham, DH1 4EB, UK.
authors.forename: Ewa
authors.initials: E
authors.lastname: Markiewicz
authors.forename: Maria
authors.initials: M
authors.lastname: Ledran
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hutchison
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D034921:Lamin Type B / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology* / Q000502:physiology; D009154:Mutation; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D034881:Nuclear Lamina / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D034904:Lamin Type A; D034921:Lamin Type B; D008565:Membrane Proteins; D016160:Retinoblastoma Protein; C093413:lamina-associated polypeptide 2