Distinct role of protein phosphatase 2A subunit Cα in the regulation of E-cadherin and β-catenin during development

Protein phosphatase 2A (PP2A) plays central roles in development, cell growth and transformation. Inactivation of the gene encoding the PP2A catalytic subunit Cα by gene targeting generates a lethal embryonic phenotype. No mesoderm is formed in Cα−/− embryos. Here, we found that during normal early embryonic development Cα was predominantly present at the plasma membrane whereas the highly homologous isoform Cβ was localized to the cytoplasm and nuclei, suggesting the inability of Cβ to compensate for vital functions of Cα in Cα−/− embryos. In addition, PP2A was found in a complex containing the PP2A substrates E-cadherin and β-catenin. In Cα−/− embryos, E-cadherin and β-catenin were redistributed from the plasma membrane to the cytosol. Cytosolic concentrations of β-catenin were low. Our results suggest that Cα is required for stabilization of E-cadherin/β-catenin complexes at the plasma membrane.