The linkage of adherens junctions to the actin cytoskeleton is essential for cell adhesion. The contribution of the cadherin-catenin complex to the interaction between actin and the adherens junction remains an intensely investigated subject that centres on the function of α-catenin, which binds to cadherin through β-catenin and can bind F-actin directly or indirectly. Here, we delineate regions within Drosophila α-Catenin (α-Cat) that are important for adherens junction performance in static epithelia and dynamic morphogenetic processes. Moreover, we address whether persistent α-catenin-mediated physical linkage between cadherin and F-actin is crucial for cell adhesion and characterize the functions of α-catenin monomers and dimers at adherens junctions. Our data support the view that monomeric α-catenin acts as an essential physical linker between the cadherin-β-catenin complex and the actin cytoskeleton, whereas α-catenin dimers are cytoplasmic and form an equilibrium with monomeric junctional α-catenin.

α-catenin is a key mechanosensor that forms force-dependent interactions with F-actin, thereby coupling the cadherin-catenin complex to the actin cytoskeleton at adherens junctions (AJs). However, the molecular mechanisms by which α-catenin engages F-actin under tension remained elusive. Here we show that the α1-helix of the α-catenin actin-binding domain (αcat-ABD) is a mechanosensing motif that regulates tension-dependent F-actin binding and bundling. αcat-ABD containing an α1-helix-unfolding mutation (H1) shows enhanced binding to F-actin in vitro. Although full-length α-catenin-H1 can generate epithelial monolayers that resist mechanical disruption, it fails to support normal AJ regulation in vivo. Structural and simulation analyses suggest that α1-helix allosterically controls the actin-binding residue V796 dynamics. Crystal structures of αcat-ABD-H1 homodimer suggest that α-catenin can facilitate actin bundling while it remains bound to E-cadherin. We propose that force-dependent allosteric regulation of αcat-ABD promotes dynamic interactions with F-actin involved in actin bundling, cadherin clustering, and AJ remodeling during tissue morphogenesis.

KAP plays an essential role in Kinesin II function, which is required for the axoneme growth and maintenance of the cilia in Drosophila type I sensory neurons. However, the flagellar assembly in Drosophila spermatids does not require Kinesin II and is independent of IFT.

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

The scaffolding protein anillin recruits septins to the cleavage furrow and constrains actomyosin contractility. Expression of E-cadherin suppresses the cytokinesis defects caused by anillin knockdown and stabilizes F-actin in the furrow, thereby providing an alternate means of coupling the actomyosin ring to the plasma membrane during cytokinesis.