Abstract
Keratins are the main cytoskeletal proteins of epithelial cells and changes in the expression of keratins have contributed to the evolutionary adaptation of epithelia to different environments. Keratin K24 was proposed to be a differentiation marker of epidermal keratinocytes but the significance of K24 expression in the epidermis versus other tissues has remained elusive. Here, we show by RT-PCR, western blot, and immunofluorescence analyses that K24 is highly expressed in the epithelium of the cornea whereas its expression levels are significantly lower in other stratified epithelia including in the epidermis. To investigate the evolutionary history of K24, we screened the genome sequences of vertebrates for orthologs of the human KRT24 gene. The results of this comparative genomics study suggested that KRT24 originated in a common ancestor of amniotes and that it was lost independently in three clades of mammals, i.e. camels, cetaceans, and a subclade of pinnipeds comprising eared seals and the walrus. Together, the results of this study identify K24 as component of the cytoskeleton in the human corneal epithelium and reveal previously unknown differences of keratin gene content among mammalian species.
Highlights
Keratins are intermediate filament (IF) proteins that form the cytoskeleton of epithelial cells[1,2,3,4]
Very low amounts of KRT24 mRNA were found in the epidermis (Fig. 2a), previous reports had suggested a role of KRT24 in differentiation of epidermal keratinocytes
The expression of KRT24 resembled that of KRT3 (Fig. 2c) and KRT12 (Fig. 2d), i.e. the established marker keratins of the differentiated corneal epithelium[24,25], and was opposite to the expression of KRT10, a marker of epidermal differentiation (Fig. 2e)
Summary
Keratins are intermediate filament (IF) proteins that form the cytoskeleton of epithelial cells[1,2,3,4]. Keratins K5 and K14 are co-expressed in the basal layer of stratified epithelia, and K1 and K10 are co-expressed in the suprabasal layers of the epidermis to form heterodimers. K2 is expressed in human suprabasal epidermis[15] so that the presence of both K1:K10 and K2:K10 dimers in the same cells causes complexity in the cytoskeleton of differentiated keratinocytes. KRT24 and KRT25 belong to a type I keratin gene subcluster that is characterized by expression in differentiated cells within the suprabasal layers of stratified epithelia or epithelial appendages (Fig. 1). Correspondence and requests for materials should be addressed to L.E. predominant expression of human KRT24 in differentiated corneal epithelial cells and for differential conservation and loss of KRT24 orthologs among mammals
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