Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin.
Wnt-1 homologs have been identified in invertebrates and vertebrates and play important roles in cellular differentiation and organization. In Drosophila, the products of the segment polarity genes wingless (the Wnt-1 homolog) and armadillo participate in a signal transduction pathway important for cellular boundary formation in embryonic development, but functional interactions between the proteins are unknown. We have examined Wnt-1 function in mammalian cells in which armadillo (beta-catenin and plakoglobin) is known to bind to and regulate cadherin cell adhesion proteins. We show that Wnt-1 expression results in the accumulation of beta-catenin and plakoglobin. In addition, binding of beta-catenin to the cell adhesion protein, cadherin, is stabilized, resulting in a concomitant increase in the strength of calcium-dependent cell-cell adhesion. Thus, a consequence of the functional interaction between Wnt-1 and armadillo family members is the strengthening of cell-cell adhesion, which may lead to the specification of cellular boundaries.
Hinck
L
L
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, California 94305-5426.
Nelson
W J
WJ
Papkoff
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D051180:Desmoplakins; D004285:Dogs; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D007668:Kidney; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism*; D015534:Trans-Activators; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin; D051185:gamma Catenin
D000906:Antibodies; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D009842:Oligopeptides; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin; D051185:gamma Catenin; D011505:Protein-Tyrosine Kinases