Regulation of Lethal giant larvae by Dishevelled

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.

Sfrp5 coordinates foregut specification and morphogenesis by antagonizing both canonical and noncanonical Wnt11 signaling

“…For example, Wnt5a-and Sfrp3-mediated PCP signaling controls proximal-distal polarity of sensory cells in the mouse inner ear epithelium (Qian et al 2007). The PCP pathway also regulates apical-basal cell polarity in the Xenopus ectoderm (Dollar et al 2005). In contrast to these examples where PCP signaling is essential to maintain a polarized epithelium, we show that Sfrp5 is required to repress PCP activity in order to establish a polarized foregut epithelium.…”

Control of tumourigenesis by the Scribble/Dlg/Lgl polarity module

“…In Xenopus and Drosophila, Lgl can act downstream of the Frizzled receptor through the binding of Lgl to Dishevelled (Dvl), a key regulator of canonical and noncanonical planar cell polarity (PCP) Wnt signalling pathways (Dollar et al, 2005). In this study, Dvl was required for Lgl localization at the cortex in Drosophila and Xenopus cells, and therefore for Lgl function in apicobasal cell polarity.…”

Cell polarity protein Lgl2 is lost or aberrantly localized in gastric dysplasia and adenocarcinoma: an immunohistochemical study

“…Lgl2 expression was limited to the basolateral cell domain, consistent with localization of Lgl in epithelial cells of model organisms. 19,25 The intensity of staining progressively increased from the base of the gastric pits, where less-differentiated cells are located, to the mucosal surface, suggesting that Lgl2 expression is a feature of more differentiated cells.…”

“…[26][27][28] It might be significant that ectopic activation of Wnt signaling interferes with membranous localization of Lgl, with concomitant loss of its activity. 25 This effect is mediated by Disheveled, an essential intracellular mediator of Wnt signaling, which associates with Lgl and is required for its stability and proper localization. 25 In summary, the localization of Lgl2 to the basolateral cell domain in normal gastric epithelium is consistent with its proposed function in control of cell polarity.…”

“…25 This effect is mediated by Disheveled, an essential intracellular mediator of Wnt signaling, which associates with Lgl and is required for its stability and proper localization. 25 In summary, the localization of Lgl2 to the basolateral cell domain in normal gastric epithelium is consistent with its proposed function in control of cell polarity. We have shown that the loss of expression of Lgl2 or its aberrant localization is closely associated with gastric epithelial dysplasia and gastric adenocarcinoma.…”