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M‐cadherin Mediates Myogenic Differentiation by Suppressing Id2 via beta‐catenin
Author(s) -
Wang Yan,
Always Stephen E.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.959.11
Subject(s) - c2c12 , beta catenin , cadherin , microbiology and biotechnology , wnt signaling pathway , transcription factor , myocyte , catenin , downregulation and upregulation , cellular differentiation , biology , myogenesis , myosin , chemistry , signal transduction , cell , gene , biochemistry
The purpose of this study was to determine if M‐cadherin mediates myogenic differentiation by modulating β‐catenin/Canonical Wnt signaling and suppressing Id2 transcription. C2C12 myoblasts were serum starved to induce myogenic differentiation. Myotube formation was confirmed by immunofluorescent staining of myosin heavy chain and calculation of the fusion index. M‐cadherin expression was either knocked‐down via RNA interference or overexpressed via transient transfection of M‐cadherin construct. Phospho‐ and total β‐catenin and GSK‐3β and total Id2 protein expression were measured by immunoblotting. C2C12 myoblasts had greater myogenic differentiation at high cell density than at low cell density in response to serum starvation. At high cell density, GSK‐3β‐dependent inhibitory phosphorylation of β‐catenin was increased and this was accompanied by downregulation of Id2 expression (both mRNA and protein), which could be rescued by knocking down M‐cadherin expression, resulting in reduced myogenic differentiation in response to serum starvation. Conversely, overexpression of M‐cadherin had the opposite effect. These data suggest that M‐cadherin mediates myogenic differentiation of C2C12 myoblasts by suppressing Id2 transcription via modulating β‐catenin transcription activity. Supported by NIH AG021530