aPKC, Crumbs3 and Lgl2 control apicobasal polarity in early vertebrate development

Abstract

In early vertebrate development, apicobasally polarised blastomeres divide to produce inner non-polarised cells and outer polarised cells that follow different fates. How the polarity of these early blastomeres is established is not known. We have examined the role of Crumbs3, Lgl2 and the apical aPKC in the polarisation of frog blastomeres. Lgl2 localises to the basolateral membrane of blastomeres, while Crumbs3 localises to the apical and basolateral membranes. Overexpression aPKC and Crumbs3 expands the apical domain at the expense of the basolateral and repositions tight junctions in the new apical-basolateral interface. Loss of aPKC function causes loss of apical markers and redirects basolateral markers ectopically to the apical membrane. Cell polarity and tight junctions, but not cell adhesion,are lost and outer polarised cells become inner-like apolar cells. Overexpression of Xenopus Lgl2 phenocopies the aPKCknockout, suggesting that Lgl2 and aPKC act antagonistically. This was confirmed by showing that aPKC and Lgl2 can inhibit the localisation of each other and that Lgl2 rescues the apicalisation caused by aPKC. We conclude that an instrumental antagonistic interaction between aPKC and Lgl2 defines apicobasal polarity in early vertebrate development.

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

“…17,18 Mutual inhibition of aPKC and Lgl has been shown to maintain complementary apical and basal cortical domains. 19,20 Mutations of lgl, scrib, or dlg in Drosophila lead not only to loss of polarized cell phenotype, but also to hyperproliferation, tumor formation, invasiveness, broad dispersal of tumor cells reminiscent of metastasis and tumor transplantability, all characteristics of a malignant neoplasm. 2,6 That loss of cell polarity is a significant factor in malignant progression was also shown in a genetic screen performed in Drosophila to find mutations sufficient to transform noninvasive tumors into invasive ones.…”

“…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.…”

Mouse prickle1 , the homolog of a PCP gene, is essential for epiblast apical-basal polarity

“…6 A-D and Fig. S7), and PKC protein was decreased mostly in central domain, which indicated partial loss of the AB polarity (26) (Fig. 6 G and L).…”

“…To investigate this, we examined the distribution of the apical determinant aPKC, an important molecule for oriented divisions and AB polarity in many systems (3,26). In the mpk1 Ϫ/Ϫ epiblast, the localization of PKC was aberrant compared with its localization in the control (Fig.…”

Regulation of epithelial cell polarity by PAR-3 depends on Girdin transcription and Girdin–Gαi3 signaling

“…In addition, by binding to PAR-3, the LIMK2 and Tiam1 actin cytoskeleton regulatory proteins and the Sec 8 exocyst protein (also known as EXOC4) have been implicated in epithelial cell polarization (Bryant et al, 2010;Macara, 2005, 2006;Zuo et al, 2009). Moreover, the Lgl tumor suppressor protein (for which there are two isoforms in mammals, LLGL1 and LLGL2) negatively regulates the tripartite PAR-3-aPKC-PAR-6 complex by competing with PAR-3 for binding to the aPKC-PAR-6 complex (Chalmers et al, 2005;Hutterer et al, 2004;Yamanaka et al, 2006Yamanaka et al, , 2003. These results show that the PAR-aPKC complex has a central role in establishing epithelial cell polarity through coordinating regulatory proteins of the cytoskeletal and vesicular transport systems.…”