Document Detail

M-cadherin-inhibited phosphorylation of ß-catenin augments differentiation of mouse myoblasts.
MedLine Citation:
PMID:  23138569     Owner:  NLM     Status:  MEDLINE    
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.
Yan Wang; Junaith S Mohamed; Stephen E Alway
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-11-09
Journal Detail:
Title:  Cell and tissue research     Volume:  351     ISSN:  1432-0878     ISO Abbreviation:  Cell Tissue Res.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-04     Completed Date:  2013-06-05     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  0417625     Medline TA:  Cell Tissue Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  183-200     Citation Subset:  IM    
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MeSH Terms
Cadherins / metabolism*
Cell Count
Cell Differentiation
Cell Fusion
Glycogen Synthase Kinase 3 / antagonists & inhibitors,  metabolism
Muscle Development
Mutant Proteins / metabolism
Myoblasts / enzymology,  metabolism*,  pathology*
RNA Interference
Subcellular Fractions / metabolism
TCF Transcription Factors / metabolism
Wnt Signaling Pathway
beta Catenin / chemistry,  genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/Cadherins; 0/Mutant Proteins; 0/TCF Transcription Factors; 0/beta Catenin; 142845-03-2/M-cadherin; EC synthase kinase 3 beta; EC Synthase Kinase 3

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