Integrated activity of PDZ protein complexes regulates epithelial polarity.
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.
Bilder
David
D
Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. bilder@socrates.berkeley.edu
Schober
Markus
M
Perrimon
Norbert
N
D000483:Alleles; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009703:Nucleoside-Phosphate Kinase / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C404683:Scrib protein, Drosophila; C400774:baz protein, Drosophila; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; C444479:sdt protein, Drosophila