Keratins
Keratins are the intermediate filament proteins that are expressed in the cytoplasm of epidermal cells. They are expressed in highly specific patterns related to the epithelial type and stage of cellular differentiation. About half of all keratins are restricted to the various compartments of hair follicles.
In keratinocytes, keratins appear to have a well defined function, that is, formation of high-strenght filamentous bundles that provides rigidity to the keratinocyte. Keratin filaments are important structural stabilizers of epidermal cells and contribute also to the stability of the whole epidermis and of the jonction between the epidermis and the dermis by being inserted at desmosomes , hemidesmosomes and corneodesmosomes.
Keratins may be separated into two groups according to their biochemical properties, type I or acidic keratins (keratins K9-K20 and Ha trichocyte keratins) and type II basic keratins (keratins K1-K8 and Hb trichocyte keratins. In contrast to the other intermediate filaments proteins, they only can constitute their filamentous stage by heteropolymeric pair formation of type I and type II (1:1) molecules.
A consensus nomenclature has been proposed that accommodates functional genes and pseudogenes and offers the incorporation of keratins from other mammalian species. This nomenclature is divided into three categories : (1) epithelial keratins, (2) hair keratins, (3) keratin pseudogenes. In humans, 54 functional keratin genes exist. There are 28 type I keratin genes (17 epithelial keratins and 11 hair keratins) and 26 type II keratin genes (20 epithelial keratins and 6 hair keratins).
In the basal layer, keratinocytes express the keratin pair K5 and K14. The functional importance of K5 and K14 for the physical stability of the epidermis has become clearly evident by the recognition that dominant-negative mutations of the K5 or the K14 gene cause the hereditary blistering skin disease epidermolysis bullosa simplex.The presence of mutated K5 or K14 results in increased fragility of the basal keratinocytes so that even mild physical trauma leads to intraepidermal cytolysis of basal cells and the formation of fluid-filled blisters.
K15 seems completely restricted to the basal cell layer of epidermis where it can form heteropolymeric filaments with K5. K15 expression in basal cells is downregulated in activated epidermal keratinocytes such as in organotypic cultures and in hyperproliferation or upon wounding.
Overall, K1 and K10 can be regarded as “keratinization markers” of keratinocytes. As the cells move out of the proliferative compartment, K5 and K14 are down-regulated while the differentiation-specific keratins, K1 and K10 are expressed. These suprabasal keratins account for 85% of the total protein of the fully differentiated squames that are sloughed from the skin surface. Ultrastructurally, keratin filaments composed of the pair K1/K10 form particularly dense bundles that contribute to the mechanical integrity to the cells and the whole epidermis. In addition, however, there seem to exist further functional roles, as experimental data have demonstrated that K10 specifically inhibits proliferation and cell cycle progression of keratinocytes and loss of K10 leads to increased keratinocyte turnover. The importance for epidermal integrity is underscored by the fact that point mutations in K1 and K10 are associated with the blistering disorder epidermolytic hyperkeratosis/bullous congenital ichthyosiform erythroderma, initially presenting with skin blisters but later with thickened ichthyotic skin . As expected, the suprabasal cells become fragmented easily and, in addition, the epidermis becomes hyperproliferative and hyperkeratotic.
The type-II keratin K6 and the type-I keratin K16 are constitutive keratins of stratified epithelia built up by keratinocytes of relatively high proliferative state such as mucosal tissues, palmoplantar epidermis, and certain skin appendages and are absent in interfollicular epidermis of hairy skin. On the other hand, they are “stress-inducible” keratins in interfollicular epidermis, being rapidly switched on e.g. after injury and UV -irradiation or being present also in inflammation and in hyperproliferative disorders. In man, mutations in K6a or K16 have been proven to give rise to the hereditary disorder pachyonychia congenita type 1 (Jadassohn–Lewandowsky form) that manifests with thickened nails, palmoplantar hyperkeratosis.
The type I keratin K9 is abundantly and highly specifically expressed in terminally differentiating keratinocytes of palmoplantar epidermis, albeit with an heterogeneous expression. At other body sites, there may be extremely sparse and focal expression in upper epidermal layers. Thus K9 forms a pair with K1. Mutations in the K9 gene are associated with a disorder of the skin of the palms and soles, epidermolytic palmoplantar keratoderma, which manifests itself as cytolysis and epidermal thickening. K9 expression appears associated with the need particular of a mechanical reinforcement of the tissue.
K2 (formerly K2e) is lately synthesized during maturation of epidermal keratinocytes and probably contributes to terminal cornification. It is widely distributed over most body sites, in the uppermost epidermal layers (upper stratum spinosum, stratum granulosum) to a variable extent.
Articles
Mots-clés dans le même groupe
Autres groupes de mots-clés
Site réalisé avec SPIP 3.0.17 + AHUNTSIC
Visiteurs connectés : 24