A new Drosophila APC homologue associated with adhesive zones of epithelial cells

Adenomatous polyposis coil protein (APC) is an important tumour suppressor in the human colon epithelium. In a complex with glycogen synthase kinase-3 (GSK-3), APC binds to and destabilizes cytoplasmic ('free') beta-catenin. Here, using a yeast two-hybrid screen for proteins that bind to the Drosoph ila beta-catenin homologue, Armadillo, we identify a new Drosophila APC hom ologue, E-APC. E-APC also binds to Shaggy, the Drosophila GSK-3 homologue. Interference with E-APC function produces embryonic phenotypes like those o f shaggy mutants. Interestingly, E-APC is concentrated in apicolateral adhe sive zones of epithelial cells, along with Armadillo and E-cadherin, which are both integral components of the adherens junctions in these zones. Vari ous mutant conditions that cause dissociation of E-APC from these zones als o obliterate the segmental modulation of free Armadillo levels that is norm ally induced by Wingless signalling. We propose that the Armadillo-destabil izing protein complex, consisting of E-APC, Shaggy, and a third protein, Ax in, is anchored in adhesive zones, and that Wingless signalling may inhibit the activity of this complex by causing dissociation of E-APC from these z ones.