Defective cell-cell adhesion in the epidermis.
The disastrous effects of loss of epidermal cell adhesion are epitomized by the life-threatening blistering skin diseases pemphigus foliaceus and pemphigus vulgaris. Clinical and experimental observations show that loss of cell adhesion is induced by these patients' autoantibodies. Pemphigus foliaceus antigen is desmoglein 1 (dsg-1), a desmosomal transmembrane glycoprotein limited in distribution to stratified squamous epithelia. It is linked to plakogoblin, a desmosomal plaque protein. Molecular cloning has shown that desmogleins are members of the cadherin gene superfamily. The originally described cadherins (e.g. E-cadherin) are transmembrane, calcium-dependent, homophilic adhesion molecules. Pemphigus vulgaris antigen is a 130 kDa glycoprotein also linked to plakoglobin. Molecular cloning has shown that pemphigus vulgaris antigen is also a desmoglein, dsg-3. Antibodies against pemphigus vulgaris antigen subdomains homologous to the binding subdomains of classical cadherins cause loss of epidermal cell adhesion, which suggests that desmogleins mediate adhesion, although direct evidence for this is lacking. The extracellular domain of pemphigus vulgaris antigen cannot substitute in function for that of E-cadherin. Future studies should address the cell biological function of desmogleins.
Stanley
J R
JR
Dermatology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015820:Cadherins / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D051184:Desmoglein 3; D004817:Epidermis / Q000503:physiopathology*; D006801:Humans; D010392:Pemphigus / Q000276:immunology / Q000503:physiopathology; D012871:Skin Diseases / Q000503:physiopathology*
D001323:Autoantibodies; D015820:Cadherins; D015815:Cell Adhesion Molecules; C071894:DSG3 protein, human; D051184:Desmoglein 3