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The cell–cell and cell–basement membrane adhesion in the epidermis provides the skin with its resistance against environmental influences; epidermal integrity is required for protection of the entire organism against mechanical, physical, or microbial insults. The major cellular structures involved are the desmosomes at cell–cell junctions in the epidermis and the hemidesmosome–basement membrane adhesion complexes and related structures at the dermal–epidermal junction. Ultrastructurally, the hemidesmosome closely resembles one-half of the desmosome; however, at the molecular level, these two structures are distinct. Both represent specifically organized assemblies of intracellular and transmembrane molecules. The desmosome anchors cytoskeletal filaments to cell–cell junctions, and the hemidesmosome anchors cytoskeletal filaments of basal epithelial cells to the basement membrane. Our knowledge of the desmosomal, hemidesmosomal, and basement membrane molecules has expanded drastically in recent years due to the great power of both molecular genetics and proteomics. After keratinocyte transmembrane proteins were initially identified as autoantigens in pemphigus and pemphigoid, a multitude of molecules have now been characterized at both protein and gene levels, and their expression, regulation, and functions have been discerned. The antigenic epitopes in different autoimmune blistering skin diseases have been carefully mapped and, to date, mutations in at least 24 different genes have been shown to underlie heritable disorders of epidermal or epidermal–dermal adhesion in humans and mice. Morphologic, molecular, and functional aspects of these adhesion structures are delineated in this chapter.
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Ultrastructure of Desmosomes
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The desmosome (or macula adherens) is the major cell adhesion junction of the epidermis, serving to anchor apposing keratinocyte cell surface membranes to the intracellular keratin intermediate filament network. Desmosomes are present in almost all epithelial tissues, including the oropharynx, gut, liver, heart, lung, bladder, kidney, prostate, thymus, cornea, and central nervous system, although the desmosomal protein isoforms and intermediate filament proteins vary by cell type.1 The primary role of desmosomes in epidermal cell adhesion is evidenced by the histologic findings in epidermal spongiosis, or intercellular edema, in which adjacent keratinocytes remain attached to each other only at desmosomal ...