Characterization of full-length and proteolytic cleavage fragments of desmoglein-2 in native human colon and colonic epithelial cell lines

Abstract

The desmosomal cadherin desmoglein-2 (Dsg2) is a transmembrane cell adhesion protein that is widely expressed in epithelial and non-epithelial tissues, such as the intestine, epidermis, testis, and heart. Dsg2 has been shown to regulate numerous cellular processes, including proliferation and apoptosis, and we have previously reported that intracellular fragments of Dsg2 promote apoptosis in colonic epithelial cells. While several studies have shown that both the extracellular and intracellular domains of Dsg2 can be targeted by proteases, identification of these putative Dsg2 fragments in colonic epithelial cells has not been performed. Here, we report that the mouse monoclonal antibody (mAb) AH12.2 binds to the first extracellular domain of Dsg2. Using this antibody along with previously described mAb against the extracellular (6D8) and intracellular (DG3.10) domains of Dsg2, we characterize the expression and identify the cleavage fragments of Dsg2 in colonic epithelial cells. This study provides a detailed description of the extracellular and intracellular Dsg2 cleavage fragments that are generated in the simple epithelium of the colon and will guide future studies examining the relationship of these fragments to cellular fate and disease states.