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PMID: 10893270 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Wnt/frizzled-2 signaling induces aggregation and adhesion among cardiac myocytes by increased cadherin-beta-catenin complex.

The Journal of cell biology ·Vol. 150 ·No. 1 ·2000-07-10 ·Pages 225-41

Toyofuku T, Hong Z, Kuzuya T, Tada M, Hori M

Abstract

Wingless is known to be required for induction of cardiac mesoderm in Drosophila, but the function of Wnt family proteins, vertebrate homologues of wingless, in cardiac myocytes remains unknown. When medium conditioned by HEK293 cells overexpressing Wnt-3a or -5a was applied to cultured neonatal cardiac myocytes, Wnt proteins induced myocyte aggregation in the presence of fibroblasts, concomitant with increases in beta-catenin and N-cadherin in the myocytes and with E- and M-cadherins in the fibroblasts. The aggregation was inhibited by anti-N-cadherin antibody and induced by constitutively active beta-catenin, but was unaffected by dominant negative and dominant positive T cell factor (TCF) mutants. Thus, increased stabilization of complexed cadherin-beta-catenin in both cell types appears crucial for the morphological effect of Wnt on cardiac myocytes. Furthermore, myocytes overexpressing a dominant negative frizzled-2, but not a dominant negative frizzled-4, failed to aggregate in response to Wnt, indicating frizzled-2 to be the predominant receptor mediating aggregation. By contrast, analysis of bromodeoxyuridine incorporation and transcription of various cardiogenetic markers showed Wnt to have little or no impact on cell proliferation or differentiation. These findings suggest that a Wnt-frizzled-2 signaling pathway is centrally involved in the morphological arrangement of cardiac myocytes in neonatal heart through stabilization of complexed cadherin- beta-catenin.

MeSH Terms
Animals Animals, Newborn Cadherins/metabolism Cell Adhesion/drug effects Cell Aggregation/drug effects Cell Differentiation/drug effects Cell Division/drug effects Cell Size/drug effects Cells, Cultured Culture Media, Conditioned/pharmacology Cytoskeletal Proteins/metabolism Fibroblasts/cytology,metabolism Gene Expression Humans Macromolecular Substances Models, Biological Multigene Family Myocardium/cytology,metabolism Proteins/genetics,metabolism,pharmacology Proto-Oncogene Proteins/genetics,metabolism,pharmacology Rats Signal Transduction/drug effects Trans-Activators Wnt Proteins Wnt-5a Protein Wnt3 Protein Wnt3A Protein beta Catenin
Chemicals
CTNNB1 protein, human Cadherins Ctnnb1 protein, rat Culture Media, Conditioned Cytoskeletal Proteins Macromolecular Substances Proteins Proto-Oncogene Proteins Trans-Activators WNT3A protein, human WNT5A protein, human Wnt Proteins Wnt-5a Protein Wnt3 Protein Wnt3A Protein beta Catenin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Toyofuku T
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan. toyofuku@mr-path.med.osaka-u.ac.jp
Hong Z
Kuzuya T
Tada M
Hori M
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.150.1.225
Email
toyofuku@mr-path.med.osaka-u.ac.jp
Published
2000-07-10
Pages
225-41
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2185559
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.150.1.225 PMC Full Text View journal details
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