Despite the presumed importance of
desmoglein, a 160-kDa
glycoprotein, in desmosome formation and its possible involvement in certain blistering
skin diseases, the precise location and function of this
protein have not yet been firmly established. We describe here the characterization of a new
monoclonal antibody, AE23, against an extracellular
epitope of
desmoglein. Both the AE23
epitope and another
epitope, defined by the previously characterized DG3.4 antibody, reside on a 160-kDa human epidermal
desmoglein as evidenced by their identical solubility profile, their coexistence in a 130-kDa
desmoglein degradative product, their coadsorption by an AE23 immunoaffinity column, and the identical changes in the two
antigens' electrophoretic mobility after air oxidation and deglycosylation. The AE23
epitope is resistant to various
endoglycosidases, suggesting that
sugar moieties are not involved. Characterization of several proteolytic fragments of this epidermal
desmoglein enabled us to map the DG3.4
epitope to a 96-kDa intracellular domain and the AE23
epitope to an extracellular domain flanked by the plasma membrane and the distal N-glycosylation site(s). However, these two
epitopes do not always coexist on the same
desmoglein molecule. For example, tissue surveys showed that although the DG3.4
epitope is present in the
desmogleins of all epithelial cell types, the AE23
epitope is limited to normal keratinocytes. Moreover, electron microscopic localization data indicate that whereas the DG3.4
epitope is detected in the submembranous plaques of desmosomes, the AE23
epitope is present in the intercellular space of both desmosomal and nondesmosomal areas. These results raise the possibility that there exist several biochemically closely related
isoforms of
desmoglein, one (AE23+/DG3.4+) restricted to epidermal desmosomes, one (AE23+/DG3.4-) uniformly distributed along the keratinocyte cell surface, and another (AE23-/DG3.4+) present in desmosomes of simple epithelia and basal cells of cultured keratinocytes. The uniform distribution of at least one
desmoglein-related
antigen in the intercellular space of keratinocytes coupled with the realization that different
isoforms of
desmogleins form a subfamily of
cadherins suggest that
desmoglein(s) may play a more general role in keratinocyte adhesion than previously appreciated.