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KEYWORDS

Desmosome, focal adhesion, hemidesmosome, basement membrane, epidermal dermal adhesion, desmoglein, desmocollin, desmoplakin, envoplakin, periplakin, plakoglobin, plakophilin, plectin, integrin, BP180, BP230, collagen, laminin, nidogen, perlecan, pemphigus, pemphigoid, proteoglycan, epidermolysis bullosa, hypotrichosis, keratoderma

AT-A-GLANCE

AT-A-GLANCE

  • The adhesive structures in the skin include desmosomes, focal adhesions, hemidesmosomes, basement membranes and dermal fibril networks.

  • Desmosomes are primarily responsible for epidermal adhesion.

  • The major components of desmosomes are the desmosomal cadherins (desmogleins and desmocollins), plakins (desmoplakin, envoplakin, and periplakin), and armadillo family proteins (plakoglobin and plakophilins).

  • Hemidesmosomes are responsible for epidermal-dermal adhesion.

  • The hemidesmosomal components comprise plakin homologs, integrins, and collagenous transmembrane proteins.

  • All basement membranes contain collagen IV, laminins, nidogens, heparan sulfate proteoglycans, and fibulins.

  • Functional specificity of basement membranes is provided by additional tissue-specific glycoproteins.

  • In addition to their structural roles, desmosomes, hemidesmosomes, and the epidermal basement membrane are biologically active in cellular signaling.

  • The dermal-epidermal junction is continuous with the extracellular matrix in the papillary dermis and thus attaches the epidermis with the dermis. The pliability and tenacity of the dermis are provided by a highly organized extracellular matrix that is also biologically active in cellular signaling.

  • Mutations in the genes encoding the above proteins cause hereditary skin diseases, ranging from hypotrichosis and keratoderma to epidermolysis bullosa and Kindler syndrome.

  • Protein components of desmosomes, hemidesmosomes, and epidermal basement membrane are targeted in autoimmune blistering diseases of the pemphigus or pemphigoid group.

INTRODUCTION

The cell–cell and cell–basement membrane adhesion in the epidermis, and the cell-matrix adhesion in the dermis provide 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 2 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 as a result of 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, as of this writing, mutations in at least 24 different genes have been shown to underlie heritable disorders of epidermal or epidermal–dermal adhesion in humans and mice. This chapter will describe the morphologic, molecular, and functional aspects of these adhesion structures.

EPIDERMAL ADHESION

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