Critical role of the Rb family in myoblast survival and fusion Journal Article


Authors: Ciavarra, G.; Ho, A. T.; Cobrinik, D.; Zacksenhaus, E.
Article Title: Critical role of the Rb family in myoblast survival and fusion
Abstract: The tumor suppressor Rb is thought to control cell proliferation, survival and differentiation. We recently showed that differentiating Rb-deficient mouse myoblasts can fuse to form short myotubes that quickly collapse through a mechanism involving autophagy, and that autophagy inhibitors or hypoxia could rescue the defect leading to long, twitching myotubes. Here we determined the contribution of pRb relatives, p107 and p130, to this process. We show that chronic or acute inactivation of Rb plus p107 or p130 increased myoblast cell death and reduced myotube formation relative to Rb loss alone. Treatment with autophagy antagonists or hypoxia extended survival of double-knockout myotubes, which appeared indistinguishable from control fibers. In contrast, triple mutations in Rb, p107 and p130, led to substantial increase in myoblast death and to elongated bi-nuclear myocytes, which seem to derive from nuclear duplication, as opposed to cell fusion. Under hypoxia, some rare, abnormally thin triple knockout myotubes survived and twitched. Thus, mutation of p107 or p130 reduces survival of Rb-deficient myoblasts during differentiation but does not preclude myoblast fusion or necessitate myotube degeneration, whereas combined inactivation of the entire Rb family produces a distinct phenotype, with drastically impaired myoblast fusion and survival. © 2011 Ciavarra et al.
Keywords: controlled study; gene mutation; nonhuman; cell proliferation; animal cell; mouse; phenotype; animal tissue; cell death; cell survival; embryo; protein depletion; cell differentiation; hypoxia; tumor suppressor gene; autophagy; protein family; retinoblastoma protein; protein p107; protein p130; cell fusion; myoblast; myotube; muscle cell
Journal Title: PLoS ONE
Volume: 6
Issue: 3
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2011-03-10
Start Page: e17682
Language: English
DOI: 10.1371/journal.pone.0017682
PROVIDER: scopus
PMCID: PMC3053373
PUBMED: 21423694
DOI/URL:
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 23 June 2011" - "Art. No.: e17682" - "Source: Scopus"
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