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

Abstract

α-catenin associates the cadherin–catenin complex with the actin cytoskeleton. α-catenin binds to β-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 αE-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 α-catenin, in particular during development, are not well understood. We have generated mutations in Drosophila α- Catenin (α- Cat ) to investigate α-Catenin function in this model, and to establish a setup for testing α-Catenin-related constructs in α- Cat -null mutant cells in vivo. Our analysis of α- 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 α- Cat loss-of-function phenotype in embryos but not in ovaries, suggesting negative regulatory interactions between α-Catenin and the Arp2/3 complex in some tissues. We also show that the α- Cat mutant phenotype can be rescued by the expression of a DE-cadherin::α-Catenin fusion protein, which argues against an essential cytosolic, cadherin-independent role of Drosophila α-Catenin.