Segregation of myoblast fusion and muscle-specific gene expression by distinct ligand-dependent inactivation of GSK-3ß.

N.A.M. Pansters, A.L.J. van der Velden, M.C.J.M. Kelders, H. Laeremans, A.M.W.J. Schols, R.C.J. Langen

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Abstract

Myogenic differentiation involves myoblast fusion and induction of muscle-specific gene expression, which are both stimulated by pharmacological (LiCl), genetic, or IGF-I-mediated GSK-3beta inactivation. To assess whether stimulation of myogenic differentiation is common to ligand-mediated GSK-3beta inactivation, myoblast fusion and muscle-specific gene expression were investigated in response to Wnt-3a. Moreover, crosstalk between IGF-I/GSK-3beta/NFATc3 and Wnt/GSK-3beta/beta-catenin signaling was assessed. While both Wnt-3a and LiCl promoted myoblast fusion, muscle-specific gene expression was increased by LiCl, but not by Wnt-3a or beta-catenin over-expression. Furthermore, LiCl and IGF-I, but not Wnt-3a, increased NFATc3 transcriptional activity. In contrast, beta-catenin-dependent transcriptional activity was increased by Wnt-3a and LiCl, but not IGF-I. These results for the first time reveal a segregated regulation of myoblast fusion and muscle-specific gene expression following stimulation of myogenic differentiation in response to distinct ligand-specific signaling routes of GSK-3beta inactivation.
Original languageEnglish
Pages (from-to)523-535
Number of pages13
JournalCellular and Molecular Life Sciences
Volume68
Issue number3
DOIs
Publication statusPublished - Feb 2011

Keywords

  • Wnt-3 alpha
  • GSK-3
  • beta-catenin
  • Myogenic differentiation
  • NFAT
  • Lithium
  • IGF-I
  • GLYCOGEN-SYNTHASE KINASE-3-BETA
  • WNT SIGNAL-TRANSDUCTION
  • ADULT SKELETAL-MUSCLE
  • BETA-CATENIN
  • MYOGENIC DIFFERENTIATION
  • SATELLITE CELLS
  • IN-VITRO
  • MYOTUBE HYPERTROPHY
  • NEGATIVE REGULATOR
  • NUCLEAR-FACTOR

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