Immunological identification and characterization of the desmosomal cadherin Dsg2 in coupled and uncoupled epithelial cells and in human tissues.

Cells of epithelia, but also of certain other tissues such as myocardium and the dendritic reticulum of lymph node follicles, are interconnected by numerous intercellular junctions termed desmosomes. These are characterized by a set of transmembrane glycoproteins, i.e. the desmosomal cadherins, desmoglein(s) and desmocollin(s). Using cDNA-derived hybridization probes, we have previously shown that different desmogleins exist (Dsg1-3) and that only one Dsg isoform, Dsg2, is found in diverse kinds of tissues, tumors and cultured cell lines whereas the synthesis of Dsg1 and Dsg3 is much more restricted, primarily to stratified epithelia [51]. We now report immunocytochemical results obtained with a series of monoclonal and polyclonal antibodies specific for either the aminoterminal extracellular portion or the carboxyterminal cytoplasmic segment of Dsg2. These antibodies detect Dsg2 in all tissues possessing desmosomes, including human stratified and single-layered polar epithelia, as well as non-epithelial tissues such as myocardium and lymph node follices. They also react with the desmosomes of carcinomas and of diverse cultured epithelium-derived cell lines. Moreover, antibodies specific for extracellular domain regions of Dsg2 react with the "half-desmosomes" present on the surfaces of uncoupled intact epithelial cells. Remarkably, in stratified squamous epithelia the Dsg2-reaction is not homogeneous, as this glycoprotein is detected only in the basal cell layer and appears to be absent from suprabasal strata. The potential value of Dsg2-specific antibodies in histology and in tumor diagnosis as well as in studies of the mechanisms desmosomal cell coupling is discussed.