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 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.
Townsley
F M
FM
Laboratory of Molecular Biology, Hills Road, CB2 2QH, Cambridge, UK.
Bienz
M
M
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
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