p120-catenin Is Essential for N-cadherin-mediated Formation of Proper Junctional Structure, thereby Establishing Cell Polarity in Epithelial Cells

Abstract

ABSTRACT. The role of p120-catenin in the function of classical cadherins is still enigmatic despite various studies. To elucidate its role, we examined the effect of p120-catenin on the N-cadherin-mediated localization of junctional proteins in epithelial cells in this study. Cadherin-deficient MIA PaCa-2 epithelial cells did not show linear localization of tight junction proteins ZO-1 and occludin. When N-cadherin was expressed in these cells, however, the resultant transfectant cells revealed strong cell adhesion activity and linear localization of ZO-1, occludin, and N-cadherin in the lateral membrane. When the p120-catenin-binding site of N-cadherin was disrupted, the linear localization of ZO-1 and occludin disappeared, and the mutant N-cadherin became localized more diffusely in the transfectant, although the cell adhesion activity did not change much. Knockdown of p120-catenin also resulted in the very weak localization of ZO-1 and occludin. A similar effect of p120-catenin on the localization of junctional proteins was obtained under more dynamic conditions in a wound healing assay. Moreover, p120-catenin was essential for the regulation of centrosome orientation in this healing assay. Taken together, the present data indicate that p120-catenin is essential for N-cadherin-mediated formation of proper junctional structures and thereby the establishment of the cell polarity. Similar results were obtained when Ecadherin mutants comparable to those of N-cadherin were used, suggesting that p120-catenin plays the same role in the function of other classical cadherins.

The Cdc42 Effector Kinase PAK4 Localizes to Cell-Cell Junctions and Contributes to Establishing Cell Polarity

“…Using a polyclonal anti-PAK4 antibody [14], we observed that PAK4 was strongly enriched at cell-cell junctions in U2OS, Panc-1 and MDCK cells (Fig 1A), and in none of these cells did we find co-staining with focal adhesion markers. The PAK4 signal at cell-cell junctions overlapped but did not colocalize precisely with the adherens junction marker p120-catenin (Fig 1B), which binds to conventional cadherins [45]. …”

N-cadherin-based adherens junction regulates the maintenance, proliferation, and differentiation of neural progenitor cells during development

“…Various reports have observed that loss of a-catenin, b-catenin, or p120-catenin perturbs the integrity of AJ and destroys the adhesion. [55][56][57][58] Three subtypes of a-catenin, aE, aN, and aT, are known.…”

“…67,73 According to the site of Numb, N-cadherin-based AJ is formed in the sub-apical region. 67,73 Numb is known to interact with p120-catenin, 58,77 so p120 catenin may be involved in the localization of N-cadherin-based AJ by Numb. , p120-catenin (p120), a-catenin (a), and a cytoskeleton, F-actin are connected to each other to construct AJ.…”

Making Heads or Tails of It: Cell–Cell Adhesion in Cellular and Supracellular Polarity in Collective Migration

“…The asymmetric distribution of cadherin-based adherens junctions resulting from their absence at the front is a distinguishing feature of leader cells and is sufficient to induce front -rear polarization of the cytoskeleton and the cytoplasm in vivo and in vitro (Desai et al 2009;Dupin et al 2009;Ozaki et al 2010;Dumortier et al 2012;Ng et al 2012;Oubaha et al 2012;Weberet al 2012). …”

“…The mechanisms that underlie cadherin-dependent front -rear polarization depend on the activity of cdc42, Rac, and PI3K, and the interaction of cell-cell junctions with the actin cytoskeleton (Desai et al 2009;Ozaki et al 2010;Dumortier et al 2012) and appear quite conserved as they were shown in both epithelial and nonepithelial cells, typically downstream from E-cadherin and N-cadherin, respectively. However, detailed analysis of these pathways is complex owing to the fact that many signaling pathways, in particular Rho GTPases, control both front -rear polarity, as discussed previously, and cell-cell adhesion (Fig.…”