The Role of Keratins in Epidermal Development and Homeostasis—Going Beyond the Obvious

Abstract

(Cyto)-Keratins are structural proteins of epithelial cells that can be divided into two subgroups, type 1 and type 2 keratins, based on biochemical properties such as molecular weight and isoelectric point. In vitro and in vivo, type 1 and type 2 keratins polymerize to form hetero-polymeric intermediate filaments (IF). IF are abundant in stratified epithelia, in particular the suprabasal layers of the epidermis. They connect to desmosomes (Cheng and Koch, 2004) at cell– cell junctions, and to hemidesmosomes (Nievers et al, 1999) at the interface of epidermis and dermis, establishing a three-dimensional network of fibrous proteins that cross the epidermis. It is widely accepted that IF are indispensable for the normal development and maintenance of stratified epithelia. Furthermore, animal models have established a cause–effect relationship between mutations in epidermal keratin and cell fragility disorders. Often, keratin missense mutations lead to a collapse of the IF network that causes cytolysis in response to even minor mechanical stress. In humans, f.i., mutations in the epidermal keratins K14 can lead to epidermolysis bullosa simplex, whereas mutations in K10 can lead to epidermolysis hyperkeratosis (for a more detailed discussion of the various keratin disorders, see Irvine and McLean, 1999).