Transglutaminases in skin epidermis

Skin functions as a stable, physical and chemical barrier from environmental influences. The cornified cell envelope (CE) is a critical structure for barrier function at the outermost layer of the skin epidermis. For CE formation in terminal keratinocyte differentiation, covalent cross-linking of constituting proteins such as involucrin, loricrin, small proline-rich protein is essential. This reaction requires transglutaminase (TGase), which is a calcium-dependent enzyme catalyzing an intermolecular isopeptide bond formation between proteins. Among the nine TGases that have been identified in humans, TGases 1, 3, and 5 are known to participate in CE formation. Both TGases 1 and 3 are activated by limited proteolysis during keratinocyte differentiation. These enzymes contribute cooperatively in sequential cross-linking of the substrates. Therefore, disorder of the TGase activity results in an irregular phenotype in the skin. In this review, the expression, regulation, and function of these TGases in the skin epidermis are focused.