title: The F-box protein Slmb restricts the activity of aPKC to polarize epithelial cells.
abstract: The Par-3/Par-6/aPKC complex is the primary determinant of apical polarity in epithelia across animal species, but how the activity of this complex is restricted to allow polarization of the basolateral domain is less well understood. In Drosophila, several multiprotein modules antagonize the Par complex through a variety of means. Here we identify a new mechanism involving regulated protein degradation. Strong mutations in supernumerary limbs (slmb), which encodes the substrate adaptor of an SCF-class E3 ubiquitin ligase, cause dramatic loss of polarity in imaginal discs accompanied by tumorous proliferation defects. Slmb function is required to restrain apical aPKC activity in a manner that is independent of endolysosomal trafficking and parallel to the Scribble module of junctional scaffolding proteins. The involvement of the Slmb E3 ligase in epithelial polarity, specifically limiting Par complex activity to distinguish the basolateral domain, points to parallels with polarization of the C. elegans zygote.
authors: Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720-3200, USA.
authors: Lara C
authors: LC
authors: Skwarek
authors: Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720-3200, USA.
authors: Sarah L
authors: SL
authors: Windler
authors: Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720-3200, USA.
authors: Geert
authors: G
authors: de Vreede
authors: Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
authors: Gregory C
authors: GC
authors: Rogers
authors: Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720-3200, USA bilder@berkeley.edu.
authors: David
authors: D
authors: Bilder
mesh_terms: D000483:Alleles; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology; D011992:Endosomes / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D044783:F-Box Proteins / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008247:Lysosomes / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D011493:Protein Kinase C / Q000378:metabolism*; D021381:Protein Transport; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D044783:F-Box Proteins; C110233:slmb protein, Drosophila; D044767:Ubiquitin-Protein Ligases; C115015:PKC-3 protein; D011493:Protein Kinase C
keywords: Drosophila; Epithelia; Par; Polarity; Tumor; Ubiquitin ligase