IDENTIFICATION OF THE UBIQUITOUS HUMAN DESMOGLEIN, DSG2, AND THE EXPRESSION CATALOG OF THE DESMOGLEIN SUBFAMILY OF DESMOSOMAL CADHERINS

Desmosomes are junctions between epithelial, myocardiac, and certain o ther kinds of cells. They represent plasma membrane domains enriched i n specific transmembrane glycoproteins, notably desmoglein (Dsg) and d esmocollin (Dsc), both of which have recently been identified as membe rs of the larger family of Ca2+-dependent cell adhesion molecules, the cadherins. Previously described forms of desmoglein have been isolate d as proteins and cloned as cDNAs from epidermis and related stratifie d epithelia but have not been detected in the majority of other desmos ome-containing tissues and cell culture lines. Here we present the com plete cDNA-derived amino acid (as) sequence of a different desmoglein polypeptide, termed Dsg2 (1069 aa, mol wt 116,760) and its precursor m olecule (1117 aa, mol wt 122,384), which occurs in all human and bovin e desmosome-producing tissues, tumors, and cell lines examined, epithe lial as well as nonepithelial ones. We conclude that Dsg2, the largest molecule in this protein family, is the fundamental desmoglein common to all desmosome-possessing tissues, including simple epithelia and m yocardium, and many cell cultures. Furthermore, in several tissues and cell lines Dsg2 is the only Dsg isoform detected so far. By contrast, the epidermal isoforms Dsg1 and Dsg3 are restricted to certain specia lized epithelia, mostly stratified squamous ones. The importance of th e junction-specific cadherin Dsg2 in tissue formation and carcinogenes is as well as in the development of autoimmune diseases of the Pemphig us type is discussed. In addition, we propose to use Dsg2 as a general marker common to all epithelial cells and tumors and to use the speci fic pattern of occurrence of Dsg and Dsc isoforms as an additional cri terion for cell typing in tumor diagnosis. (C) 1994 Academic Press, In c.