Molecular complexity of the cutaneous basement membrane zone.
Ultrastructural examination of the cutaneous basement membrane zone (BMZ) reveals the presence of several attachment structures, which are critical for integrity of the stable association of epidermis and dermis. These include hemidesmosomes which extend from the intracellular compartment of the basal keratinocyte to the underlying basement membrane where they complex with anchoring filaments, thread-like structures traversing the lamina lucida. At the lower portion of dermal-epidermal attachment zone, anchoring fibrils extend from the lamina densa to the papillary dermis, where they associate with basement membrane-like structures, known as anchoring plaques. Molecular cloning of the cutaneous BMZ components has allowed elucidation of the structural features of the proteins which constitute these attachment structures. Specifically, hemidesmosomes have been shown to consist of at least four distinct proteins. The intracellular hemidesmosomal inner plaque is comprised of the 230-kD bullous pemphigoid antigen (BPAG1), and plectin, a high-molecular weight cytomatrix protein, encoded by the corresponding gene, PLEC1. The transmembrane component of the hemidesmosomes consists of the 180-kD bullous pemphigoid antigen (BPAG2), a collagenous protein also known as type XVII collagen (COL17A1), as well as of the basal keratinocyte-specific integrin alpha 6 beta 4. The anchoring filaments consist predominantly of laminin 5 with three constitutive subunit polypeptides, the alpha 3, beta 3 and gamma 2 chains, which is associated with laminin 6 with the chain composition alpha 3, beta 1 and gamma 1. Also associated with anchoring filaments is a novel protein, ladinin, which serves as autoantigen in the linear IgA disease, and the corresponding gene, LAD1, has been mapped to human chromosome 1. Finally, the major, if not the exclusive, component of anchoring fibrils is type VII collagen, encoded by the gene (COL7A1) which consists of 118 distinct exons, the largest number of exons in any gene published thus far. Collectively, the cutaneous basement membrane zone is a complex continuum of macromolecules which form a network providing the stable association of the epidermis to the underlying dermis. Thus, genetic lesions resulting in abnormalities in any part of this network could result in a blistering skin disease, such as epidermolysis bullosa.
Uitto
J
J
Department of Dermatology, Jefferson Medical College, Philadelphia, PA 19107, USA.
Pulkkinen
L
L
D015703:Antigens, CD / Q000502:physiology; D001324:Autoantigens / Q000502:physiology; D001485:Basement Membrane / Q000737:chemistry / Q000648:ultrastructure; D002352:Carrier Proteins; D003094:Collagen / Q000502:physiology; D003598:Cytoskeletal Proteins; D003896:Desmosomes / Q000737:chemistry; D000071821:Dystonin; D004817:Epidermis / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D030342:Genetic Diseases, Inborn / Q000235:genetics; D006801:Humans; D039503:Integrin alpha6; D039663:Integrin beta4; D007381:Intermediate Filament Proteins / Q000502:physiology; D007797:Laminin / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D051190:Plectin; D012867:Skin / Q000648:ultrastructure*; D012872:Skin Diseases, Vesiculobullous / Q000378:metabolism; D000097805:Collagen Type XVII
D015703:Antigens, CD; D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D016326:Extracellular Matrix Proteins; D039503:Integrin alpha6; D039663:Integrin beta4; D007381:Intermediate Filament Proteins; D007797:Laminin; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D051190:Plectin; D000097805:Collagen Type XVII; C486268:DST protein, human; C105230:Lad1 protein, mouse; C495332:PLEC protein, human