An unusual type-II 70-kilodalton keratin protein of mouse epidermis exhibiting postnatal body-site specificity and sensitivity to hyperproliferation

Rentrop, Martin; Nischt, Roswitha; Knapp, Bernhard; Schweizer, Jürgen; Winter, Hermelita

doi:10.1111/j.1432-0436.1987.tb00066.x

Cited by 27 publications

(30 citation statements)

References 38 publications

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“…K6 and K16 are expressed in the posterior segments (5a, 48). K13 is expressed in the orthokeratinized anterior segments, and K4 and K13 are both expressed in the interpapillary suprabasal epithelium (11,49). While expression of K5Pgal90 paralleled that of K13 in tongue, ,B-Gal was not detected in other internal stratified epithelia, e.g., esophagus and forestomach, where this keratin is also expressed (60,71).…”

Section: Resultsmentioning

confidence: 99%

Probing keratinocyte and differentiation specificity of the human K5 promoter in vitro and in transgenic mice.

Byrne¹,

Fuchs²

1993

Mol. Cell. Biol.

127

132

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K5 and K14 are interesting in that they are broadly expressed in most stratified epithelial tissues (45). In these tissues, the pair is expressed in mitotically active basal keratinocytes, as judged by in situ hybridizations and/or immunohistochemical localization of epidermis (32, 42, 51), rodent forestomach (60), tongue (11), and various other stratified and pseudo-stratified epithelia (42). In addition, K5 has been detected histologically in a number of epithelial cells, including human thymic reticulum, the ORS, sebaceous glands, and both basal and myoepithelial cells of eccrine sweat glands and salivary glands (42). Indeed, an important and unifying feature of basal keratinocytes appears to be their unique ability to express K5 and K14, irrespective of body location (45). Given that cell-typespecific expression of KS and K14 genes appears to be at the transcriptional level (33, 69), the promoters of these genes * Corresponding author. seem to display an insensitivity to the varied environments of keratinocytes.Little is known about the molecular mechanisms which govern the complex expression of genes in the keratinocyte. Given that (i) K5 and K14 account for up to 30% of total protein of mitotically active keratinocytes and (ii) the tissuespecific expression of these proteins is regulated transcriptionally (33, 69), K5 and K14 genes provide ideal tools for investigating these regulatory mechanisms. The human KS and K14 genes have been cloned and sequenced (33,37). Cell type specificity of the KS promoter has been suggested from tissue culture studies (22,46), although the K14 promoter is promiscuously expressed in a number of cell types in vitro (30,75). While the in vivo behavior of the K5 promoter has not yet been explored, 2,100 bp of the K14 promoter is sufficient to direct expression of heterologous genes to the basal cells of stratified epithelia in transgenic mice (7,73,74).A number of recent studies have begun to focus on identifying putative regulatory domains and transcription factors that may be involved in expression of either endogenous or viral genes in keratinocytes (3,4,8,9,20,22,24,29,30,35,37,46,52,54,65,66,72,75). Thus far, only a few nuclear factors that both are restricted in their tissue specificity and appear to participate in conferring keratinocytespecific gene expression have been identified. One of these, AP2, has been implicated broadly in the regulation of endogenous and viral genes that are typically expressed in keratinocytes (29,30,40,54,65,66). However, AP2 does not appear to be sufficient for keratinocyte specificity on its own (29).The aim of this work was to explore the regulatory mechanisms involved in controlling keratinocyte-specific gene expression in culture and in transgenic animals. We 3176

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Section: Resultsmentioning

confidence: 99%

Probing keratinocyte and differentiation specificity of the human K5 promoter in vitro and in transgenic mice.

Byrne¹,

Fuchs²

1993

Mol. Cell. Biol.

127

132

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“…Monomeric K6 might be undetectable or washed out from the living epidermal layers during processing of the sections but be detectable again in the stratum corneum because of crosslinking to the cornified envelope scaffold. We also checked for expression levels of K2, normally restricted to specific skin regions such as palm and sole epidermis (Rentrop et al, 1987), and for K15, and found that neither of these keratins was upregulated in Krt1 2/2 ;Krt10 2/2 back skin epidermis ( Fig. 4G) and that their epidermal expression patterns were the same as in the wild type (from immunofluorescence analysis; data not shown).…”

Section: /2mentioning

confidence: 99%

“…In the specialized thicker epidermis of soles and palms K2 and K9 are additionally expressed to complement the K1/K10 (where K1/K10 indicates the dimer between K1 and K10) 5 network. In contrast to humans, where K2 is more widely expressed, in mice K2 expression is restricted to foodpad, tail and ear epidermis (Rentrop et al, 1987). Keratins K6, K16 and K17 are normally restricted to hair follicles but upon wound healing and in hyperproliferative conditions their expression is strongly upregulated in the interfollicular epidermis (Kirfel et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Deletion of K1/K10 does not impair epidermal stratification but affects desmosomal structure and nuclear integrity

Wallace

Roberts-Thompson

Reichelt

2012

Journal of Cell Science

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SummaryKeratins K1 and K10 are the most abundant proteins in the upper epidermis where they polymerize to form intermediate filaments (IFs). In addition to their well-established function in providing epidermal stability, K1/K10 (i.e. the dimer between K1 and K10) IFs are supposed to be important for terminal epidermal differentiation and barrier formation. It was previously shown that the imbalanced deletion of one of the partner keratins, K10, disturbed epidermal homoeostasis, although stability was provided by compensatory upregulation of K5/K14, which formed IFs together with the remaining K1. Here, we show that deletion of both partner keratins, K1 and K10, results in lethal postnatal skin fragility in mice. Krt1 2/2 ;Krt10 2/2 mice revealed that K1/K10 IFs are unexpectedly dispensable for epidermal stratification. Although the stratum corneum was less compact and cornified envelope differentiation was impaired, a dye exclusion assay showed that the development of a functional water barrier was surprisingly independent from the presence of K1/K10 IFs. The deletion of K1/K10 was not compensated by any other keratin pair such as the basal epidermal keratins K5/K14, and electron microscopy revealed total absence of IFs in the suprabasal epidermis. Although plakoglobin was unchanged, the expression of the desmosomal proteins desmoplakin, desmocollin 1 and desmoglein 1 were altered and suprabasal desmosomes were smaller in Krt1 2/2 ;Krt10 2/2 than in wild-type epidermis suggesting an involvement of K1/K10 IFs in desmosome dynamics. Furthermore, Krt1 2/2 ;Krt10 2/2 mice showed premature loss of nuclei during epidermal differentiation and lower levels of emerin, lamin A/C and Sun1, revealing a previously unknown function for IFs in maintaining nuclear integrity in the upper epidermis.

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“…A unique 70-kD type II keratin, ultimately identified as K2e, had been initially reported in keratin extracts from ear, footpad and tail [Rentrop et al, 1987;Herzog et al, 1994]. To determine if the nipple and the ventral K14-PTHrP skin expressed the same site-specific keratin, we probed a Western blot of keratin extracts with a K2e monoclonal antibody.…”

Section: Resultsmentioning

confidence: 99%

“…The most abundant keratin detected by 2-dimensional gel electrophoresis in the regionally specialized epidermis of the mouse (the ear, tail and footpad) is K2e; however, this protein is not expressed in skin of the murine trunk Mahler/Gocken/Brojan/Childress/Spandau/ Foley [Rentrop et al, 1987;Darmon and Blumenberg, 1993;Herzog et al, 1994]. K2e is expressed in the suprabasal cells of the inner footpad regions, whereas the unique palmar/plantar keratin 9 [Schweizer et al, 1989] expression is found on the apical portion of the footpad which produces the very prominent stratum corneum [Schweizer, 1993].…”

Section: Discussionmentioning

confidence: 99%

Keratin 2e: A Marker for Murine Nipple Epidermis

Mahler

Gocken

Brojan

et al. 2004

Cells Tissues Organs

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Mesenchyme-derived signals influence the unique keratinization and appendage formation programs in specialized skin regions. Interactions between primary mammary mesenchyme and epidermal cells result in the formation of the nipple; however, it is unclear whether this represents a site of regionally specialized epidermis. We profiled the ultrastructure and keratin expression of the murine nipple, and the ventral skin of the K14-parathyroid hormone-related protein (PTHrP) transgenic mouse, which models nipple formation. We found the murine nipple and ventral K14-PTHrP epidermis display expanded suprabasal and granular layers, as well as a thickened cornified layer compared to ventral skin of wild-type littermates. We also observed increased levels of filaggrin in extracts from the ventral epidermis of the K14-PTHrP mouse when compared to that of wild-type littermates. Keratin 2e, previously reported to be expressed in various specialized epidermal sites in the mouse, is expressed in the nipple and the ventral skin of the K14-PTHrP mouse. Keratinocytes grown from the ventral epidermis of the K14-PTHrP mouse or wild-type littermates exhibited identical expression of epidermal markers in vitro, suggesting that the modulated differentiation profile observed in the nipple or the ventral K14-PTHrP skin was dependent on interactions with fibroblasts. The lack of appendages, altered stratification pattern and expression of a specialized keratin suggests that the murine nipple is an example of regionally specialized epidermis.

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An unusual type-II 70-kilodalton keratin protein of mouse epidermis exhibiting postnatal body-site specificity and sensitivity to hyperproliferation

Cited by 27 publications

References 38 publications

Probing keratinocyte and differentiation specificity of the human K5 promoter in vitro and in transgenic mice.

Probing keratinocyte and differentiation specificity of the human K5 promoter in vitro and in transgenic mice.

Deletion of K1/K10 does not impair epidermal stratification but affects desmosomal structure and nuclear integrity

Keratin 2e: A Marker for Murine Nipple Epidermis

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