Actin-dependent membrane association of a Drosophila epithelial APC protein and its effect on junctional Armadillo

Background: The adenomatous polyposis coli (APC) protein is an important tu mour suppressor in the colon. It promotes the destabilisation of free cytop lasmic beta -catenin (the vertebrate homologue of the Drosophila protein Ar madillo), a critical effector of the Wnt signalling pathway. The beta -cate nin protein is also a component of adherens junctions, linking these to the actin cytoskeleton. In Drosophila epithelial cells, the ubiquitous form of APC, known as E-APC, is associated with adherens junctions. This associati on appears to be necessary for E-APC to function in destabilising Armadillo . Results: Using actin-depolymerising drugs, we established that an intact ac tin cytoskeleton is required for the association of E-APC with adherens jun ctions in the Drosophila embryo. From an analysis of profilin mutants, whos e actin cytoskeleton is disrupted, we found that E-APC also requires actin filaments to associate with adhesive cell membranes in the ovary. Notably, conditions that delocalised E-APC from membranes, including a mutation in E -APC itself, caused partial detachment of Armadillo from adhesive membranes . Conclusions: Actin filaments are continuously required for E-APC to be asso ciated with junctional membranes. These filaments may serve as tracks for E -APC to reach the adherens junctions. The failure of E-APC to do so appears to affect the integrity of junctional complexes.