Mutational analysis supports a core role for Drosophila α-Catenin in adherens junction function

alpha-catenin associates the cadherin-catenin complex with the actin cytoskeleton. a-catenin binds to beta-catenin, which links it to the cadherin cytoplasmic tail, and F-actin, but also to a multitude of actin-associated proteins. These interactions suggest a highly complex cadherin-actin interface. Moreover, mammalian alpha E-catenin has been implicated in a cadherin-independent cytoplasmic function in Arp2/3-dependent actin regulation, and in cell signaling. The function and regulation of individual molecular interactions of alpha-catenin, in particular during development, are not well understood. We have generated mutations in Drosophila alpha-Catenin (alpha-Cat) to investigate alpha-Catenin function in this model, and to establish a setup for testing a-Catenin-related constructs in alpha-Cat-null mutant cells in vivo. Our analysis of alpha-Cat mutants in embryogenesis, imaginal discs and oogenesis reveals defects consistent with a loss of cadherin function. Compromising components of the Arp2/3 complex or its regulator SCAR ameliorate the alpha-Cat loss-of-function phenotype in embryos but not in ovaries, suggesting negative regulatory interactions between alpha-Catenin and the Arp2/3 complex in some tissues. We also show that the alpha-Cat mutant phenotype can be rescued by the expression of a DE-cadherin::alpha-Catenin fusion protein, which argues against an essential cytosolic, cadherin-independent role of Drosophila alpha-Catenin.