Regulation of Lethal giant larvae by Dishevelled

Gretchen L. Dollar, Ursula Weber, Marek Mlodzik and Sergei Y. Sokol ()
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Gretchen L. Dollar: Mount Sinai School of Medicine
Ursula Weber: Mount Sinai School of Medicine
Marek Mlodzik: Mount Sinai School of Medicine
Sergei Y. Sokol: Mount Sinai School of Medicine

Nature, 2005, vol. 437, issue 7063, 1376-1380

Abstract: 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.

Date: 2005
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DOI: 10.1038/nature04116

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