M-cadherin-inhibited phosphorylation of ß-catenin augments differentiation of mouse myoblasts

Research output: Contribution to journalArticle

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Abstract

β-Catenin is essential for muscle development because it regulates both cadherin-mediated cell-cell adhesion and canonical Wingless and Int1 (Wnt) signaling. The phosphorylation of β-catenin by glycogen synthase kinase-3β (GSK-3β) at serine31/37/threonine41 regulates its stability and its role in canonical Wnt signaling. In this study, we have investigated whether the N-terminal phosphorylation of β-catenin is regulated by M-cadherin, and whether this regulation mediates the role of M-cadherin in myogenic differentiation. Our data show that the knockdown of M-cadherin expression by RNA interference (RNAi) in C2C12 myoblasts significantly increases the phosphorylation of β-catenin at Ser33/37/Thr41 and decreases the protein abundance of ser37/thr41-unphosphorylated active β-catenin. Furthermore, M-cadherin RNAi promotes TCF/LEF transcription activity but also blunts the initiation of the myogenic progress by Wnt pathway activator lithium chloride or Wnt-3a treatment. Knockdown of β-catenin expression by RNAi decreases myogenic induction in myoblasts. Forced expression of a phosphorylation-resistant β-catenin plasmid (S33Y-β-catenin) fails to enhance myogenic differentiation, but it partially rescues C2C12 cells from M-cadherin RNAi-induced apoptosis. These data show, for the first time, that M-cadherin-mediated signaling attenuates β-catenin phosphorylation at Ser31/37/Thr41 by GSK-3β, and that this regulation has a positive effect on myogenic differentiation induced by canonical Wnt signaling.

Original languageEnglish (US)
Pages (from-to)183-200
Number of pages18
JournalCell and Tissue Research
Volume351
Issue number1
DOIs
StatePublished - Jan 1 2013

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Catenins
Myoblasts
Phosphorylation
RNA Interference
Glycogen Synthase Kinase 3
Lithium Chloride
M-cadherin
Wnt Signaling Pathway
Muscle Development
Cadherins
Cell Adhesion
Plasmids
Apoptosis

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Cite this

M-cadherin-inhibited phosphorylation of ß-catenin augments differentiation of mouse myoblasts. / Wang, Yan; Mohamed, Junaith; Alway, Stephen.

In: Cell and Tissue Research, Vol. 351, No. 1, 01.01.2013, p. 183-200.

Research output: Contribution to journalArticle

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