Hinck L, Nelson W J, Papkoff J
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, California 94305-5426.
J Cell Biol. 1994 Mar;124(5):729-41. doi: 10.1083/jcb.124.5.729.
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.
Wnt-1同源物已在无脊椎动物和脊椎动物中被鉴定出来,并在细胞分化和组织中发挥重要作用。在果蝇中,节段极性基因无翅(Wnt-1同源物)和犰狳的产物参与了胚胎发育中对细胞边界形成至关重要的信号转导途径,但这些蛋白质之间的功能相互作用尚不清楚。我们已经在哺乳动物细胞中研究了Wnt-1的功能,在这些细胞中,已知犰狳(β-连环蛋白和桥粒斑蛋白)能结合并调节钙黏蛋白细胞黏附蛋白。我们发现Wnt-1的表达导致β-连环蛋白和桥粒斑蛋白的积累。此外,β-连环蛋白与细胞黏附蛋白钙黏蛋白的结合得以稳定,从而导致钙依赖性细胞间黏附强度随之增加。因此,Wnt-1与犰狳家族成员之间功能相互作用的一个结果是细胞间黏附增强,这可能导致细胞边界的特化。