Regulation of Lethal giant larvae by Dishevelled

Nature. 2005 Oct 27;437(7063):1376-80. doi: 10.1038/nature04116.

Abstract

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. The conserved complex of Par3, Par6 and atypical protein kinase C 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Cell Membrane / metabolism
  • Cell Polarity
  • Dishevelled Proteins
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism*
  • Ectoderm / cytology
  • Ectoderm / metabolism
  • Epithelium / metabolism
  • Female
  • Immunoprecipitation
  • Male
  • Phosphoproteins / deficiency
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Protein Kinase C / metabolism
  • Protein Transport
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Tumor Suppressor Proteins / metabolism*
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / embryology
  • Xenopus laevis / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • DVL1 protein, Xenopus
  • Dishevelled Proteins
  • Drosophila Proteins
  • FZD8 protein, Xenopus
  • LLGL1 protein, Xenopus
  • Phosphoproteins
  • Receptors, Cell Surface
  • Tumor Suppressor Proteins
  • Xenopus Proteins
  • dsh protein, Drosophila
  • l(2)gl protein, Drosophila
  • PKC-3 protein
  • Protein Kinase C