Posttranslational regulation of plakoglobin expression. Influence of the desmosomal cadherins on plakoglobin metabolic stability

Abstract

Desmosomes are adhesive intercellular junctions that act as cell surface attachment sites for intermediate filaments. The desmosomal glycoproteins, desmogleins and desmocollins, are members of the cadherin family of adhesion molecules. In addition, desmoglein has been shown to coimmunoprecipitate with the junctional protein plakoglobin. To characterize further the interaction between plakoglobin and the desmosomal cadherins, stable mouse fibroblast (L-cells) cell lines were generated that express plakoglobin, desmoglein and plakoglobin, or desmocollin and plakoglobin. L-cell lines transfected with a plasmid encoding human plakoglobin expressed plakoglobin mRNA but very little plakoglobin protein. However, plakoglobin protein was expressed at high levels in L-cells coexpressing either desmoglein or desmocollin. In addition, both desmocollin and desmoglein were found to coimmunoprecipitate with plakoglobin. The transient expression of desmoglein in L-cell lines expressing plakoglobin mRNA resulted in the formation of a complex between plakoglobin and desmoglein and in the accumulation of plakoglobin protein. Furthermore, the rate of plakoglobin protein degradation was decreased by 15-20-fold in cell lines expressing either desmoglein or desmocollin. These results demonstrate that the desmosomal cadherins posttranslationally regulate plakoglobin expression by decreasing the rate of plakoglobin degradation.