CROSS-TALK BETWEEN ADHERENS JUNCTIONS AND DESMOSOMES DEPENDS ON PLAKOGLOBIN

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 s eparate structures with different molecular make up, it is not immedia tely obvious why formation of an adherens junction is a prerequisite f or the formation of a desmosome. The adherens junction is composed of a transmembrane classical cadherin (E-cadherin and/or P-cadherin in sq uamous epithelial cells) linked to either beta-catenin or plakoglobin, which is linked to alpha-catenin, which is linked to the actin cytosk eleton. The desmosome is composed of transmembrane proteins of the bro ad cadherin family (desmogleins and desmocollins) that are linked to t he intermediate filament cytoskeleton, presumably through plakoglobin and desmoplakin. To begin to study the role of adherens junctions in t he assembly of desmosomes, we produced an epithelial cell line that do es not express classical cadherins and hence is unable to organize des mosomes, even though it retains the requisite desmosomal components. T ransfection of E-cadherin and/or P-cadherin into this cell line did no t restore the ability to organize desmosomes; however, overexpression of plakoglobin, along with E-cadherin, did permit desmosome organizati on. These data suggest that plakoglobin, which is the only known commo n component to both adherens junctions and desmosomes, must be linked to E-cadherin in the adherens junction before the cell can begin to as semble desmosomal components at regions of cell-cell contact. Although adherens junctions can form in the absence of plakoglobin, making use only of beta-catenin, such junctions cannot support the formation of desmosomes. Thus, we speculate that plakoglobin plays a signaling role in desmosome organization.