Cross-Talk between Adherens Junctions and Desmosomes Depends on Plakoglobin

Abstract

Squamous epithelial cells have both adherens junctions and desmosomes. The ability of these cells to organize the desmosomal proteins into a functional structure depends upon their ability first to organize an adherens junction. Since the adherens junction and the desmosome are separate structures with different molecular make up, it is not immediately obvious why formation of an adherens junction is a prerequisite for the formation of a desmosome. The adherens junction is composed of a transmembrane classical cadherin (E-cadherin and/or P-cadherin in squamous epithelial cells) linked to either β-catenin or plakoglobin, which is linked to α-catenin, which is linked to the actin cytoskeleton. The desmosome is composed of transmembrane proteins of the broad cadherin family (desmogleins and desmocollins) that are linked to the intermediate filament cytoskeleton, presumably through plakoglobin and desmoplakin. To begin to study the role of adherens junctions in the assembly of desmosomes, we produced an epithelial cell line that does not express classical cadherins and hence is unable to organize desmosomes, even though it retains the requisite desmosomal components. Transfection of E-cadherin and/or P-cadherin into this cell line did not restore the ability to organize desmosomes; however, overexpression of plakoglobin, along with E-cadherin, did permit desmosome organization. These data suggest that plakoglobin, which is the only known common component to both adherens junctions and desmosomes, must be linked to E-cadherin in the adherens junction before the cell can begin to assemble desmosomal components at regions of cell–cell contact. Although adherens junctions can form in the absence of plakoglobin, making use only of β-catenin, such junctions cannot support the formation of desmosomes. Thus, we speculate that plakoglobin plays a signaling role in desmosome organization.

Transfection of Keratin 18 Gene in Human Breast Cancer Cells Causes Induction of Adhesion Proteins and Dramatic Regression of Malignancy In vitro and In vivo

“…Conditions are less clear in the E-cadherin system. Here, there is no direct contact with the keratin filaments; however, the desmosomes may be influenced via plakoglobin, which is a component of both systems (30). Then, mediated by plakoglobin, the reorganizing force of the keratin filaments could extend via the desmosomes into the zonula adherens.…”

Arrhythmogenic Right Ventricular Cardiomyopathy Plakophilin-2 Mutations Disrupt Desmosome Assembly and Stability

“…A431D cells are a derivative of A431 cells that have lost expression of the classical cadherins (Eand P-cadherin) and are unable to assemble adherens junctions and desmosomes (Lewis et al 1997). Previous work in our laboratory has demonstrated that expression of many classical cadherins in A431D cells will support junction assembly (data not shown).…”

“…A431 cells express classical cadherins (E-and P-cadherin) and assemble fully functional adherens junctions and desmosomes. A431D cells are a cadherin-negative derivative of A431 cells in which classical cadherin expression is lost and these cells do not assemble cell junctions (Lewis et al 1997). Desmosome assembly is restored in A431D cells by expressing a classical cadherin and plakophilin (Wahl 2005).…”

Tyrosine residues 654 and 670 in β-catenin are crucial in regulation of Met–β-catenin interactions

“…β-Catenin also functions as a bridge between the cytoplasmic domain of cadherins and the actin-containing cytoskeleton [25,26]. β-Catenin complex with the cytoplasmic tail of Ecadherin is mostly regulated by phosphorylation at tyrosine-654, which induces β-catenin dissociation from E-cadherin, thus negatively influencing cell-cell adhesion [27].…”