Ancient origin of the gene encoding involucrin, a precursor of the cross-linked envelope of epidermis and related epithelia

Abstract

The cross-linked (cornified) envelope is a characteristic product of terminal differentiation in the keratinocyte of the epidermis and related epithelia. This envelope contains many proteins of which involucrin was the first to be discovered and shown to become cross-linked by a cellular transglutaminase. Involucrin has evolved greatly in placental mammals, but retains the glutamine repeats that make it a good substrate for the transglutaminase. Until recently, it has been impossible to detect involucrin outside the placental mammals, but analysis of the GenBank and Ensembl databases that have become available since 2006 reveals the existence of involucrin in marsupials and birds. We describe here the properties of these involucrins and the ancient history of their evolution.aves ͉ marsupial ͉ evolution ͉ glutamine repeats T he outer surface of the skin of humans and other mammals consists of dead cells, each of which contains a chemically resistant envelope. The nature of this envelope has been extensively reviewed (1, 2). Envelopes formed in cultures of epidermal cells are insoluble in ionic detergents at 100°C, but are dissolved by proteolytic enzymes (3). The envelopes are Ϸ120 Å in thickness (4) and composed of proteins heavily cross-linked by -(␥ glutamyl) lysine (isopeptide) bonds introduced by the action of transglutaminase (5). A protein ultimately incorporated into the cross-linked envelope was discovered as a soluble precursor before the activation of the cross-linking (6, 7). This precursor was named involucrin (from the Latin for envelope: involucrum) and was present only in enlarging cells undergoing terminal differentiation (8,9). Because involucrin is a substrate of transglutaminase, it is not surprising that it contains numerous glutamines capable of participating in the cross-linking reaction. Human involucrin contains 38-42 repeats of a 10 amino acid sequence, each repeat containing 3 glutamine residues (10-13).Other protein precursors of the cross-linked envelope were soon discovered (14). One had a molecular mass of 210 kDa and was later named envoplakin (15). Another had a molecular mass of 195 kDa and was later named periplakin (16). Still other precursors were discovered, including filaggrin (17), small proline-rich repeat proteins or SPRRs (18), and loricrin (19). The genes encoding most envelope precursors (but not periplakin or envoplakin) are located in the region of human chromosome 1q21, the so-called EDC or epidermal differentiation complex (20). This has been shown for involucrin (13), filaggrin (21), loricrin (22), cornifin (23), the SPRRs (24), and others (25). Other proteins encoded in the EDC, such as cornulin (26), appear late in terminal differentiation, but are not envelope precursors. Still others are precursors that are incorporated after the envelope is formed, particularly the ''late envelope proteins'' (27). It has been proposed that because involucrin, loricrin, and SPRR proteins have similar amino acid sequences in their N-terminal and C-terminal domains, they probab...

Differential Features of AIRE-Induced and AIRE-Independent Promiscuous Gene Expression in Thymic Epithelial Cells

“…The Sprr multigene family is instrumental in the formation of a cornified envelope (CE), which serves as a protective barrier in various stratified squamous epithelia (27). Moreover, we observed that genes encoding CE structural proteins, including involucrin, cornifelin, and cytokeratin 4, were also upregulated in KO cTEC (28,29). Taken together, these results suggest that Aire 2/2 cTEC acquire a more differentiated phenotype by upregulation of genes involved in CE formation.…”

Review: mapping epidermal beta-protein distribution in the lizard Anolis carolinensis shows a specific localization for the formation of scales, pads, and claws

“…The localization of betaprotein genes in the EDC of both Gallus gallus and Anolis carolinensis has been found between the loricrin gene and the involucrin-trichohyalin-like genes, and this suggests that the genes for beta-proteins derived from a modification of ancestral genes common for a precursor EDC-protein, indicated as simple EDC proteins (SEDC, Strasser et al 2014). Therefore, in sauropsid genomes, the genes coding for corneous betaproteins evolved in regions that in mammalian genomes are instead occupied by mammalian-specific genes coding for other EDC-corneous proteins (Vanhoutteghem et al 2008;Strasser et al 2014). Comparative genomics therefore further confirms that proteins formerly termed beta-keratins Fig.…”

“…The latter enable different skin derivatives such scales, claws, beaks, horns, and feathers to perform their specific functions. Recent genomic studies have also shown that genes for "beta-keratins" in both the chick and lizard are clustered within the "epidermal differentiation complex" locus (EDC), together with the genes for other corneous proteins, and are not linked to alpha-keratins loci (Vanhoutteghem et al 2008;Eckhart et al 2008;Mlitz et al 2014;Strasser et al 2014;Figs. 3 …”

“…Conversely, in the epidermis and skin derivatives of mammals (hairs, horns, claws, hooves) and in all the remaining vertebrates, the hard corneous material is formed by the combination of intermediate filament keratins with a variable number of "keratin-associated proteins" (KAPs) in skin derivatives, or with corneous proteins of the "epidermal differentiation complex" (EDC) such as filaggrin, loricrin, involucrin, small proline-rich proteins, etc. in the epidermis (Baden and Maderson 1970;Gillespie 1991;Kalinin et al 2002;Rogers 2004;Vanhoutteghem et al 2008;Bragulla and Homberger 2009;Eckhart et al 2013). In particular, in humans, while type I keratins genes are clustered in chromosome 17, those for type II keratin are in chromosome 12, and the genes of the epidermal differentiation complex are instead localized in chromosome 1 (Mischke et al 1996).…”

Derivation of keratinocytes from chicken embryonic stem cells: Establishment and characterization of differentiated proliferative cell populations

“…The other antibodies were kindly provided by Pr Danielle Dhouailly for αK-11E10 (keratin 14) (Collomb et al, 2013), by Dr Furuse for anti-occludin (Furuse et al, 1993) and by Dr Philippe Djian for anti-involucrin (Vanhoutteghem et al, 2008).…”