title: Domains controlling cell polarity and proliferation in the Drosophila tumor suppressor Scribble.
abstract: Cell polarity and cell proliferation can be coupled in animal tissues, but how they are coupled is not understood. In Drosophila imaginal discs, loss of the neoplastic tumor suppressor gene scribble (scrib), which encodes a multidomain scaffolding protein, disrupts epithelial organization and also causes unchecked proliferation. Using an allelic series of mutations along with rescuing transgenes, we have identified domain requirements for polarity, proliferation control, and other Scrib functions. The leucine-rich repeats (LRR) tether Scrib to the plasma membrane, are both necessary and sufficient to organize a polarized epithelial monolayer, and are required for all proliferation control. The PDZ domains, which recruit the LRR to the junctional complex, are dispensable for overall epithelial organization. PDZ domain absence leads to mild polarity defects accompanied by moderate overproliferation, but the PDZ domains alone are insufficient to provide any Scrib function in mutant discs. We suggest a model in which Scrib, via the activity of the LRR, governs proliferation primarily by regulating apicobasal polarity.
authors.affiliation: Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zeitler
authors.forename: Cynthia P
authors.initials: CP
authors.lastname: Hsu
authors.forename: Heather
authors.initials: H
authors.lastname: Dionne
authors.forename: David
authors.initials: D
authors.lastname: Bilder
mesh_terms: D000483:Alleles; D000818:Animals; D002352:Carrier Proteins / Q000145:classification / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D049109:Cell Proliferation; D004330:Drosophila / Q000166:cytology / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004848:Epithelium / Q000378:metabolism; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D009154:Mutation
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; C404683:Scrib protein, Drosophila