title: Actin-dependent membrane association of a Drosophila epithelial APC protein and its effect on junctional Armadillo.
abstract: BACKGROUND
  The adenomatous polyposis coli (APC) protein is an important tumour suppressor in the colon. It promotes the destabilisation of free cytoplasmic beta-catenin (the vertebrate homologue of the Drosophila protein Armadillo), a critical effector of the Wnt signalling pathway. The beta-catenin 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 association appears to be necessary for E-APC to function in destabilising Armadillo.
  
  
  RESULTS
  Using actin-depolymerising drugs, we established that an intact actin cytoskeleton is required for the association of E-APC with adherens junctions in the Drosophila embryo. From an analysis of profilin mutants, whose 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 associated 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.
authors.affiliation: Laboratory of Molecular Biology, Hills Road, CB2 2QH, Cambridge, UK.
authors.forename: F M
authors.initials: FM
authors.lastname: Townsley
authors.forename: M
authors.initials: M
authors.lastname: Bienz
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D000199:Actins / Q000378:metabolism*; D025601:Adenomatous Polyposis Coli Protein; D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D051186:Armadillo Domain Proteins; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism*; D048429:Cell Size; D003078:Colchicine / Q000494:pharmacology; D003285:Contractile Proteins; D015638:Cytochalasin D / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D019476:Insect Proteins / Q000276:immunology / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D010590:Phalloidine / Q000494:pharmacology; D051304:Profilins; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D015534:Trans-Activators; D014157:Transcription Factors
chemical_list: C118001:APC protein, Drosophila; C495305:ARM protein, Drosophila; D000199:Actins; D025601:Adenomatous Polyposis Coli Protein; D051186:Armadillo Domain Proteins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D005456:Fluorescent Dyes; D019476:Insect Proteins; D008840:Microfilament Proteins; D051304:Profilins; D013844:Thiazoles; D053778:Thiazolidines; D015534:Trans-Activators; D014157:Transcription Factors; C495737:chic protein, Drosophila; D010590:Phalloidine; D015638:Cytochalasin D; D003078:Colchicine; C037067:latrunculin A