Adherens Junction and E-Cadherin complex regulation by epithelial polarity

Abstract

E-Cadherin-based Adherens Junctions (AJs) are a defining feature of all epithelial sheets. Through the homophilic association of E-Cadherin molecules expressed on neighboring cells, they ensure intercellular adhesion amongst epithelial cells, and regulate many key aspects of epithelial biology. While their adhesive role requires these structures to remain stable, AJs are also extremely plastic. This plasticity allows for the adaptation of the cell to its changing environment: changes in neighbors after cell division, cell death, or cell movement, and changes in cell shape during differentiation. In this review we focus on the recent advances highlighting the critical role of the apico-basal polarity machinery, and in particular of the Par3/Bazooka scaffold, in the regulation and remodeling of AJs. We propose that by regulating key phosphorylation events on the core E-Cadherin complex components, Par3 and epithelial polarity promote meta-stable protein complexes governing the correct formation, localization, and functioning of AJ.

Polarity protein Par3/Bazooka follows myosin-dependent junction repositioning

“…One case that is similar to the results reported here occurs during the initial phase when two cultured cells make contact and establish polarization. In such cases, it is the formation of the small E-Cad clusters that triggers the subsequent recruitment of Baz to the contact site (Coopman and Djiane, 2016). These two cases have one feature in common: namely, that the membranes between neighbor cells are not yet apposed at the site where future junctions will form.…”

“…Among apical-basal polarity proteins, the scaffold protein Par3/Bazooka (Baz) is distinguished by a localization to the interface between the apical and basal-lateral domains, a position where cell-cell junctions also reside. Increasing evidence points to an essential role for Baz in determining junction morphology and localization (Coopman and Djiane, 2016; Tepass, 2012; West and Harris, 2016). In Drosophila embryos for example, Baz has been implicated in the formation of junctions during the initial establishment of epithelium (Harris and Peifer, 2004), in the basal shift of junctions during the folding of mature epithelium (Wang et al, 2012), and in the planar polarization of junctional components during tissue elongation (Simoes Sde et al, 2010).…”

“…In Drosophila embryos for example, Baz has been implicated in the formation of junctions during the initial establishment of epithelium (Harris and Peifer, 2004), in the basal shift of junctions during the folding of mature epithelium (Wang et al, 2012), and in the planar polarization of junctional components during tissue elongation (Simoes Sde et al, 2010). In the classic epithelium polarization models derived from mammalian cultured cells, Baz is required for the stabilization of small junction clusters, thereby marking the zone where the zonulae adherens will form (Coopman and Djiane, 2016). …”

Janus kinase 3 regulates adherens junctions and epithelial mesenchymal transition through β-catenin

“…AJs play a major role in maintaining the integrity of epithelial tissue architecture (1, 2). The plasticity of AJs has several physiological and pathophysiological implications, including morphogenesis, proliferation, migration, and differentiation during mucosal restitution (4, 5), EMT (6), and neoplastic transformation (28).…”

“…An adherens junctions (AJ) 3 is a multimolecular protein complex that connects neighboring cells, thereby maintaining epithelial tissue architecture (1, 2). AJs are created through extracellular homotypic protein–protein interactions between single-pass trans-membrane cadherin molecules.…”