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

Nature Cell Biology volume 1, pages 144–151 (1999)Cite this article

Abstract

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’) β-catenin. Here, using a yeast two-hybrid screen for proteins that bind to the Drosophila β-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.

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Figure 1: A new APC homologue and its binding to Armadillo.
Figure 2: Apical localization of E-APC.
Figure 3: Requirement of Armadillo for membrane association of E-APC during cellularization.
Figure 4: Zonula adherens mutants cause dissociation of E-APC from adhesive zones.
Figure 5: Armadillo striping is obliterated in zonula adherens mutants.
Figure 6: sgg mutants show delocalization of E-APC from adhesive zones.
Figure 7: sgg-like phenotypes caused by dsRNA interference with E-APC.

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Acknowledgements

We thank M. Bourouis for the sgg cDNA; A. González-Reyes, H. Skaer, J.-P. Vincent, A. Müller and the Developmental Studies Hybridoma Bank for antibodies and fly strains; B. Amos for help with the confocal microscopy; and M. Freeman and H. Pelham for comments on the manuscript. X.Y. was supported by a studentship from Trinity College, Cambridge.

Correspondence and requests for materials should be addressed to M.B.

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    Xiang Yu, Lucas Waltzer & Mariann Bienz

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Correspondence to Mariann Bienz.

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Yu, X., Waltzer, L. & Bienz, M. A new Drosophila APC homologue associated with adhesive zones of epithelial cells. Nat Cell Biol 1, 144–151 (1999). https://doi.org/10.1038/11064

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