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Regulation of Lethal giant larvae by Dishevelled

Nature volume 437, pages 1376–1380 (2005)Cite this article

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 targeting1,2,3,4. The conserved complex of Par3, Par6 and atypical protein kinase C5,6,7,8 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.

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Figure 1: Lgl1 modulates apical–basal polarity in superficial ectoderm.
Figure 2: Dsh is required for Lgl activity and membrane localization.
Figure 3: Lgl1 and Dsh are required for apical–basal polarity in embryonic ectoderm.
Figure 4: Fz8 alters localization and activity of Lgl.

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Acknowledgements

We thank K. Itoh, J. Green, J. LeBlanc-Straceski, B. Lake and S. Dhawan for discussions and comments on the manuscript; J. Knoblich for anti-Lgl antibody; S. Citi for anti-occludin antibodies; A. Chalmers for the immunohistochemistry protocol; B. Brott for initial work on the yeast two-hybrid screen; and A. Djiane for help with the Drosophila studies. This work was supported by NIH grants (to S.Y.S. and M.M.) and an NIH training grant (to G.L.D.).

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  1. Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, Box 1020, One Gustave L. Levy Place, New York, 10029, New York, USA

    Gretchen L. Dollar, Ursula Weber, Marek Mlodzik & Sergei Y. Sokol

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  1. Gretchen L. Dollar
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  2. Ursula Weber
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  3. Marek Mlodzik
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Correspondence to Sergei Y. Sokol.

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Supplementary information

Supplementary Figures

This file contains Supplementary Figures 1–3. Supplementary Figure 1 demonstrates specificity of anti-Lgl antibodies using western analysis of Xenopus embryo lysates. Supplementary Figure 2 shows Dsh and Lgl constructs used in this study, and immunoprecipitation experiments demonstrating Dsh and Lgl interactions in vivo. Supplementary Figure 3 shows specific depletion of Lgl1 protein in stage 10 embryos upon injection of LglMO. (DOC 467 kb)

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Dollar, G., Weber, U., Mlodzik, M. et al. Regulation of Lethal giant larvae by Dishevelled. Nature 437, 1376–1380 (2005). https://doi.org/10.1038/nature04116

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