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Integrated activity of PDZ protein complexes regulates epithelial polarity

Nature Cell Biology volume 5, pages 53–58 (2003)Cite this article

Abstract

Polarized cells contain numerous membrane domains, but it is unclear how the formation of these domains is coordinated to create a single integrated cell architecture. Genetic screens of Drosophila melanogaster embryos have identified three complexes, each containing one of the PDZ domain proteins — Stardust (Sdt), Bazooka (Baz) and Scribble (Scrib) — that control epithelial polarity and formation of zonula adherens. We find that these complexes can be ordered into a single regulatory hierarchy that is initiated by cell adhesion-dependent recruitment of the Baz complex to the zonula adherens. The Scrib complex represses apical identity along basolateral surfaces by antagonizing Baz-initiated apical polarity. The Sdt-containing Crb complex is recruited apically by the Baz complex to counter antagonistic Scrib activity. Thus, a finely tuned balance between Scrib and Crb complex activity sets the limits of the apical and basolateral membrane domains and positions cell junctions. Our data suggest a model in which the maturation of epithelial cell polarity is driven by integration of the sequential activities of PDZ-based protein complexes.

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Figure 5: A model of the embryonic epithelial polarization pathway.
Figure 1: Localization of PDZ protein complexes.
Figure 2: Epistasic analysis of dlg with sdt and baz.
Figure 3: Reduction of scrib group activity suppresses crb group phenotypes.
Figure 4: Recovery of apicobasal polarity in late crb and dlg M/Z embryos.

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Acknowledgements

We thank A. Wodarz, A. Muller and M. Peifer for providing reagents, C. Villalta for technical assistance, and B. Mathey-Prevot and reviewers for comments on the manuscript. We also thank G. Tanentzapf and U. Tepass for sharing data before publication. N.P. is an Investigator of the Howard Hughes Medical Institute. M.S. acknowledges support from Boehringer Ingelheim Fonds. D. B. acknowledges support from the American Cancer Society, the Leukemia Society of America, and the Burroughs-Wellcome Fund.

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  1. David Bilder and Markus Schober: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, 02115, MA, USA

    David Bilder, Markus Schober & Norbert Perrimon

  2. Department of Molecular and Cell Biology, University of California-Berkeley, 142 LSA #3200, Berkeley, 94720-3200, CA, USA

    David Bilder

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Correspondence to David Bilder.

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Supplementary Figure

Figure S1. scrib and dlg enhance crb gain-of-function phenotypes. (PDF 270 kb)

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Bilder, D., Schober, M. & Perrimon, N. Integrated activity of PDZ protein complexes regulates epithelial polarity. Nat Cell Biol 5, 53–58 (2003). https://doi.org/10.1038/ncb897

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