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Lookup NU author(s): Dr Maria Ledran, Professor Christopher Hutchison
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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 LAP2α 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 depbosphorylation of the retinoblastoma protein Rb. During myogenesis, Rb was rapidly and progressively dephosphorylated. Underphosphorylated Rb formed complexes with LAP2α 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.
Author(s): Markiewicz E, Ledran M, Hutchison CJ
Publication type: Article
Publication status: Published
Journal: Journal of Cell Science
Year: 2005
Volume: 118
Issue: 2
Pages: 409-420
ISSN (print): 0021-9533
ISSN (electronic): 1477-9137
Publisher: The Company of Biologists Ltd.
URL: http://dx.doi.org/10.1242/jcs.01630
DOI: 10.1242/jcs.01630
PubMed id: 15654018
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