Biology of anchoring fibrils: lessons from dystrophic epidermolysis bullosa.

Anchoring fibrils are adhesive suprastructures that ensure the connection of the epidermal basement membrane with the dermal extracellular matrix. The fibrils represent polymers of collagen VII, the major structural fibril component, but may also contain other proteins. Remarkable progress has been made in the last few years in understanding the functions of skin basement membrane components including the anchoring fibrils.

Transient bullous dermolysis of the newborn associated with compound heterozygosity for recessive and dominant COL7A1 mutations.

The neonatal skin blistering disorder transient bullous dermolysis of the newborn (TBDN) heals spontaneously or improves dramatically within the first months and years of life. TBDN is characterized by subepidermal blisters, reduced or abnormal anchoring fibrils at the dermo-epidermal junction, and electron-dense inclusions in keratinocytes. These features are partly similar to those in dystrophic epidermolysis bullosa, which is caused by defects in COL7A1 gene encoding collagen VII, the main anchoring fibril protein.

Two forms of collagen XVII in keratinocytes. A full-length transmembrane protein and a soluble ectodomain.

The cDNA sequence of human collagen XVII predicts an unusual type II transmembrane protein, but a biochemical characterization of this structure has not been accomplished yet. Using domain-specific antibodies against recombinant collagen XVII fragments, we identified two molecular forms of the collagen in human skin and epithelial cells. Full-length collagen XVII appeared as a homotrimeric transmembrane molecule of three 180-kDa alpha1(XVII) chains.