Regulation of Lethal giant larvae by Dishevelled

• Published in: Nature (London) 2005-10, Vol.437 (7063), p.1376-1380
• Main Authors: Dollar, Gretchen L., Weber, Ursula, Mlodzik, Marek, Sokol, Sergei Y.
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Animals; Biological and medical sciences; Cell Membrane - metabolism; Cell physiology; Cell Polarity; Cellular biology; Dishevelled Proteins; Drosophila melanogaster - metabolism; Drosophila Proteins - metabolism; Ectoderm - cytology; Ectoderm - metabolism; Embryos; Epithelium - metabolism; Female; Freshwater; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; Immunoprecipitation; Insects; Larvae; letter; Male; Molecular and cellular biology; multidisciplinary; Phosphoproteins - deficiency; Phosphoproteins - genetics; Phosphoproteins - metabolism; Protein Binding; Protein Kinase C - metabolism; Protein Transport; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Science; Science (multidisciplinary); Signal transduction; Tumor Suppressor Proteins - metabolism; Xenopus laevis - embryology; Xenopus laevis - metabolism; Xenopus Proteins - genetics; Xenopus Proteins - metabolism
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature04116

The establishment of polarity in many cell types depends on Lgl, the tumour suppressor product of lethal giant larvae , which is involved in basolateral protein targeting 1 , 2 , 3 , 4 . The conserved complex of Par3, Par6 and atypical protein kinase C 5 , 6 , 7 , 8 phosphorylates and inactivates Lgl at the apical surface; however, the signalling mechanisms that coordinate cell polarization in development are not well defined. Here we show that a vertebrate homologue of Lgl associates with Dishevelled, an essential mediator of Wnt signalling, and that Dishevelled regulates the localization of Lgl in Xenopus ectoderm and Drosophila follicular epithelium. We show that both Lgl and Dsh are required for normal apical–basal polarity of Xenopus ectodermal cells. In addition, we show that the Wnt receptor Frizzled 8, but not Frizzled 7, causes Lgl to dissociate from the cortex with the concomitant loss of its activity in vivo . These findings suggest a molecular basis for the regulation of cell polarity by Frizzled and Dishevelled.