Keratin Intermediate Filaments and Diseases of the Skin

Abstract

Aquestion that still challenges cell and tissue biologists is that of the driving forces that have selected for and conserved the numerous intermediate filament proteins in vertebrates. We are only beginning to understand the functions of this family of cyto-skeleton structures and we have very few experimental tools for testing comparative functions of these proteins in a satisfactory way. A major turning point came with the discoveries that mutations in keratin intermediate filament genes were responsible for a large number of inherited skin fragility disorders. These disease links showed unequivocally that intermediate filament proteins, at least in barrier epithelia like skin, provide essential stress resilience for cells in tissues. The keratin genes account for three quarters of all the intermediate filament genes identified in the human genome, and it seems highly likely that any function attributable these structural proteins will also be important for the nonkeratin intermediate filaments. Once the stress resistance function of intermediate filaments is taken as a fact, rather than a persistent speculation, this knowledge can guide further experimental analysis and design to allow us to at last move closer to understanding the biology of these enigmatic cytoskeleton filaments.