@article {836081, title = {Integrated activity of PDZ protein complexes regulates epithelial polarity.}, journal = {Nat Cell Biol}, volume = {5}, number = {1}, year = {2003}, month = {2003 Jan}, pages = {53-8}, 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.}, keywords = {Alleles, Animals, Binding Sites, Carrier Proteins, Cell Polarity, Drosophila melanogaster, Drosophila Proteins, Embryo, Nonmammalian, Epithelial Cells, Guanylate Kinase, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Membrane Transport Proteins, Nucleoside-Phosphate Kinase}, issn = {1465-7392}, doi = {10.1038/ncb897}, author = {Bilder, David and Schober, Markus and Perrimon, Norbert} }