A new Drosophila APC homologue associated with adhesive zones of epithelial cells.
Adenomatous polyposis coli 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 Drosophila beta-catenin homologue, Armadillo, we identify a new Drosophila APC homologue, E-APC. E-APC also binds to Shaggy, the Drosophila GSK-3 homologue. Interference with E-APC function produces embryonic phenotypes like those of shaggy mutants. Interestingly, E-APC is concentrated in apicolateral adhesive zones of epithelial cells, along with Armadillo and E-cadherin, which are both integral components of the adherens junctions in these zones. Various mutant conditions that cause dissociation of E-APC from these zones also obliterate the segmental modulation of free Armadillo levels that is normally induced by Wingless signalling. We propose that the Armadillo-destabilizing protein complex, consisting of E-APC, Shaggy, and a third protein, Axin, is anchored in adhesive zones, and that Wingless signalling may inhibit the activity of this complex by causing dissociation of E-APC from these zones.
Yu
X
X
MRC Laboratory of Molecular Biology, Cambridge, UK.
Waltzer
L
L
Bienz
M
M
D025601:Adenomatous Polyposis Coli Protein; D000595:Amino Acid Sequence; D000818:Animals; D051186:Armadillo Domain Proteins; D001665:Binding Sites; D002448:Cell Adhesion; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D017491:Genes, APC; D006801:Humans; D019476:Insect Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D010641:Phenotype; D012330:RNA, Double-Stranded / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D014157:Transcription Factors
C495305:ARM protein, Drosophila; D025601:Adenomatous Polyposis Coli Protein; D051186:Armadillo Domain Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D012330:RNA, Double-Stranded; D015534:Trans-Activators; D014157:Transcription Factors