Adhesion molecules. I: Keratinocyte-keratinocyte interactions; cadherins and pemphigus.

During the last few years, considerable progress has been made in our understanding of the structure and function of cadherins and of the pathophysiology of pemphigus. Cadherins are a multiple gene family of Ca(++)-dependent cell adhesion molecules with a typical single-spanning transmembrane structure. Cadherins have two major subfamilies, classic cadherin and desmosomal cadherin. Classic cadherins, including E-, P-, and N-cadherins, are characterized by a homophilic binding specificity. They localize at adherens junctions and mediate physiologic interaction with the involvement of cytoplasmic anchoring molecules, catenins, and the actin-based cytoskeleton network. Desmosomal cadherins, the desmocollins and desmogleins, localize at desmosomes and are linked to the intermediate keratin filaments network via plakoglobin and desmoplakin. Molecular cloning has demonstrated that the autoantigens of both pemphigus vulgaris and pemphigus foliaceus are members of the desmoglein subfamily of the cadherin supergene family. Thus, pemphigus is characterized as an anti-cadherin autoimmune disease. Furthermore, a baculovirus recombinant protein of pemphigus vulgaris antigen was capable of absorbing out the pathogenic autoantibodies from patients' sera, providing a possibility of antigen-specific therapeutic strategies for pemphigus.