Research
- Our Main Objectives
- Introduction to Keratin Genes and Proteins
- Assembly and Organization of Keratin Filaments
- Keratins fulfill Multiple Roles in Skin and other Epithelia
- Keratin Gene Expression in Epidermis: Basic Principles and Disease Associations
- Introduction to Skin Epithelia
- Figure 1 - Introduction to Keratins
- Table 1 - Keratin-based, Inherited Skin Bullous Disease Affecting Primarily the Epidermis
Keratins Fulfill Multiple Roles in Skin and other Epithelia
A major function shared by keratins and all other IF proteins is to endow cells and tissues with the ability to withstand mechanical trauma. This structural support function was revealed, at least in the formal sense, by studies of K5-K14 polymers in basal keratinocytes of transgenic mouse epidermis (P.A. Coulombe et al., J. Cell Biol. 1991). Loss of this function, e.g. through mutations, underlies a large variety of rare diseases that render cells and tissues unusually fragile (M.B. Omary et al., New Engl. J. Med. 2004). Disease-causing mutations in K14 and K5 decrease the physical strength of keratin IF assemblies in vitro, in a manner consistent with the cellular fragility seen in vivo (see L. Gu and P.A. Coulombe, Curr. Opin. Cell. Biol. 2007)
Whereas the discovery of keratin mutations in the context of several tissue fragility diseases dominated the 1990’s, the recent discovery of non-mechanical functions has placed the field on a novel, exciting, and significant path. Specifically, keratin IFs have been found to modulate the cellular response to specific pro-apoptotic signals in liver, extraembryonic tissue, and hair follicles of the skin. They also participate in the control of cell and tissue growth, e.g., by regulating protein synthesis or mitosis. In gut epithelia, they influence the positioning of basal bodies, organization of microtubules, and routing of specific membrane proteins to apical and basolateral domains. Keratins influence skin pigmentation, likely through an impact on melanin distribution in keratinocytes. Keratin proteins also contribute, in various ways, to the tissue response to injury and other forms of challenges, possibly through their ability to act as a phosphate sink. We (and others!) have recently reviewed this rapidly evolving area of IF biology (see L. Gu and P.A. Coulombe, Curr. Opin. Cell. Biol. 2007; S. Kim and P.A. Coulombe, Genes & Dev. 2007).
