Remodelling of the nuclear lamina and nucleoskeleton is required for skeletal muscle differentiation in vitro
Author:
Markiewicz Ewa1, Ledran Maria1, Hutchison Christopher J.1
Affiliation:
1. Integrative Cell Biology Laboratory, School of Biological and Biomedical Sciences, University of Durham, South Road, Durham, DH1 4EB, UK
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 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 dephosphorylation 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.
Publisher
The Company of Biologists
Reference56 articles.
1. Bergstrom, D. A., Penn, B. H., Strand A., Perry, R. L., Rudnicki, M. A. and Tapscott, S. J. (2002). Promoter-specific regulation of MyoD binding and signal transduction cooperate to pattern gene expression. Mol. Cell.9, 587-600. 2. Biamonti, G., Giacca, M., Perini, G., Contreas, G., Zentilin, L., Weignardt, F., Guerra, M., Della Valle, G., Saccone, S. and Riva, S. (1992). The gene for a novel human lamin maps to a highly transcribed locus of chromosome 19 which replicates at the onset of S-phase. Mol. Cell. Biol.12, 3499-3506. 3. Bonne, G., di Barletta, M. R., Varnous, S., Becane, H. M., Hammouda, E. H., Merlini, L., Muntoni, F., Greenberg, C. R., Gary, F., Urtizberea, J. A. et al. (1999). Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy. Nat. Genet.21, 285-288. 4. Brodsky, G. L., Muntoni, F., Miocic, S., Sinagra, G., Sewry, C. and Mestroni, L. (2000). Lamin A/C gene mutation associated with dilated cardiomyopathy with variable skeletal muscle involvement. Circulation101, 473-476. 5. Burke, B. and Stewart, C. L. (2002). Life at the edge: the nuclear envelope and human disease. Nat. Rev. Mol. Cell Biol.3, 575-585.
Cited by
94 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
|
|