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PMID:10893270

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Citation

Toyofuku, T, Hong, Z, Kuzuya, T, Tada, M and Hori, M (2000) Wnt/frizzled-2 signaling induces aggregation and adhesion among cardiac myocytes by increased cadherin-beta-catenin complex. J. Cell Biol. 150:225-41

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.

Links

PubMed PMC2185559

Keywords

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; Fibroblasts/metabolism; Gene Expression; Humans; Macromolecular Substances; Models, Biological; Multigene Family; Myocardium/cytology; Myocardium/metabolism; Proteins/genetics; Proteins/metabolism; Proteins/pharmacology; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins/pharmacology; Rats; Signal Transduction/drug effects; Trans-Activators; Wnt Proteins; Wnt3 Protein; Wnt3A Protein; beta Catenin

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:WNT5A

enables

GO:0005109: frizzled binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:1888513)

Seeded From UniProt

complete

MOUSE:FZD2

enables

GO:0042813: Wnt-activated receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:WNT5A

enables

GO:0005109: frizzled binding

ECO:0000314: direct assay evidence used in manual assertion

F

has_input:(MGI:MGI:1888513)

Seeded From UniProt

complete

MOUSE:WNT5A

acts_upstream_of_or_within

GO:2000049: positive regulation of cell-cell adhesion mediated by cadherin

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WNT3A

acts_upstream_of_or_within

GO:2000049: positive regulation of cell-cell adhesion mediated by cadherin

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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