Distinct role of protein phosphatase 2A subunit C alpha in the regulation of E-cadherin and beta-catenin during development

Protein phosphatase 2A (PP2A) plays central roles in development, cell grow th and transformation. Inactivation of the gene encoding the PP2A catalytic subunit C alpha by gene targeting generates a lethal embryonic phenotype. No mesoderm is formed in C alpha(-/-) embryos. Here, we Found that during n ormal early embryonic development C alpha was predominantly present at the plasma membrane whereas the highly homologous isoform C beta was localized to the cytoplasm and nuclei, suggesting the inability of C beta to compensa te for vital functions of C alpha in C alpha(-/-) embryos. In addition, PP2 A was found in a complex containing the PP2A substrates E-cadherin and beta -catenin. In C alpha(-/-) embryos, E-cadherin and beta-catenin were redistr ibuted from the plasma membrane to the cytosol. Cytosolic concentrations of beta-catenin were low. Our results suggest that C alpha is required for st abilization of E-cadherin/beta-catenin complexes at the plasma membrane. (C ) 2000 Elsevier Science Ireland Ltd. All rights reserved.