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Jürgen Schweizer - One of the best experts on this subject based on the ideXlab platform.
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characterization of human kap24 1 a cuticular Hair Keratin associated protein with unusual amino acid composition and repeat structure
Journal of Investigative Dermatology, 2007Co-Authors: Michael A. Rogers, Hermelita Winter, Lutz Langbein, Luis F Javesuarez, Anke Wollschlager, Silke Praetzelwunder, Jürgen SchweizerAbstract:In a search for genes overexpressed in human sexual Hairs, several partial complementary DNA (cDNA) sequences were isolated. Screening of a human scalp cDNA library with one fragment led to the isolation of a full-length cDNA clone, which showed identity to another known sequence, termed KAP24-1 (AB09693). Bioinformatic analysis revealed that the gene for this cDNA consisted of one exon and was located ca. 86 kb away from the chromosome 21q22.1 Keratin-associated protein (KAP) gene domain. RT-PCR analysis of a variety of organs showed that KAP24.1 was only present in human scalp. The KAP24.1 protein consisted of 254 amino acids, exhibited a high content of serine, proline, and tyrosine, but low cysteine content and possessed several carboxyterminal tyrosine-containing tandem decameric repeat structures. Evolutionary tree analysis showed no association to other KAP family members. In situ hybridization and indirect immunofluorescence microscopy studies using an antibody derived from KAP24.1 demonstrated specific expression in the middle/upper Hair cuticle. The structure of the KRTAP24, its proximity to the chromosome 21q22.1 KAP gene domain, the presence of repeat motifs in the protein and its localization in the Hair cuticle points to KAP24.1 being a novel human KAP family member.
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Keratins of the human Hair follicle
International Review of Cytology-a Survey of Cell Biology, 2005Co-Authors: Lutz Langbein, Jürgen SchweizerAbstract:Abstract Substantial progress has been made regarding the elucidation of differentiation processes of the human Hair follicle. This review first describes the genomic organization of the human Hair Keratin gene family and the complex expression characteristics of Hair Keratins in the Hair-forming compartment. Sections describe the role and fate of Hair Keratins in the diseased Hair follicle, particularly hereditary disorders and Hair follicle–derived tumors. Also included is a report on the actual state of knowledge concerning the regulation of Hair Keratin expression. In the second part of this review, essentially the same principles are applied to outline more recent and, thus, occasionally fewer data on specialized epithelial Keratins expressed in various tissue constituents of the external sheaths and the companion layer of the follicle. A closing outlook highlights issues that need to be explored further to deepen our insight into the biology and genetics of the Hair follicle.
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krtap16 characterization of a new Hair Keratin associated protein kap gene complex on mouse chromosome 16 and evidence for regulation by hoxc13
Journal of Biological Chemistry, 2004Co-Authors: Nathanael D Pruett, Jürgen Schweizer, Christopher S Potter, Luis F Javesuarez, Tatiana V Tkatchenko, Donna Jacobs, Andrei V Tkatchenko, Alexander AwgulewitschAbstract:Intermediate filament (IF) Keratins and Keratin-associated proteins (KAPs) are principal structural components of Hair and encoded by members of multiple gene families. The severe Hair growth defects observed upon aberrant expression of certain Keratin and KAP genes in both mouse and man suggest that proper Hair growth requires their spatio-temporally coordinated activation. An essential prerequisite for studying these cis-regulatory mechanisms is to define corresponding gene families, their genomic organization, and expression patterns. This work characterizes eight recently identified high glycine/tyrosine (HGT)-type KAP genes collectively designated Krtap16-n. These genes are shown to be integrated into a larger KAP gene domain on mouse chromosome 16 (MMU16) that is orthologous to a recently described HGT- and high sulfur (HS)-type KAP gene complex on human chromosome 21q22.11. All Krtap16 genes exhibit strong expression in a narrowly defined pattern restricted to the lower and middle cortical region of the Hair shaft in both developing and cycling Hair. During Hair follicle regression (catagen), expression levels decrease until expression is no longer detectable in follicles at resting stage (telogen). Since isolation of the Krtap16 genes was based on their differential expression in transgenic mice overexpressing the Hoxc13 transcriptional regulator in Hair, we examined whether bona fide Hoxc13 binding sites associated with these genes might be functionally relevant by performing electrophoretic mobility shift assays (EMSAs). The data provide evidence for sequence-specific interaction between Hoxc13 and Krtap16 genes, thus supporting the concept of a regulatory relationship between Hoxc13 and these KAP genes.
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expression of Hair Keratins in the adult nail unit an immunohistochemical analysis of the onychogenesis in the proximal nail fold matrix and nail bed
British Journal of Dermatology, 2004Co-Authors: Christophe Perrin, Lutz Langbein, Jürgen SchweizerAbstract:Summary Background Recently, the expression profiles of the members of the complex Hair Keratin family have been determined in the human anagen Hair follicle. In contrast, the details of Hair Keratin expression in the human nail unit are poorly known. Objectives In order to fill this gap, we have performed an immunohistochemical study of the adult human nail unit by means of specific antibodies against nine Hair Keratins of both types (hHa2, hHb2, hHa5, hHb5, hHa1, hHb1, hHb6, hHa4 and hHa8) as well as three epithelial Keratins (K5, K17 and K10). Methods Formalin-fixed paraffin sections of adult nails were examined using monoclonal and polyclonal Keratin antibodies, respectively. Longitudinal as well as transverse sections were investigated. Results Our study revealed two types of epithelial tissue compartments in the nail unit. The first comprised the eponychium and hyponychium and the nail bed, which expressed only epithelial Keratins. While Keratins K5, K17 (basal) and K10 (suprabasal) were found in the orthoKeratinizing eponychium and hyponychium, throughout, the nail bed epithelium expressed only K5 and K17. The second type comprised the apical and ventral matrix which exhibited a mixed pattern of epithelial and Hair Keratin expression. Thus, K5 and K17 were expressed in the entire multilayered basal cell compartment of the apical and ventral matrix; however, in the latter, K5 and K17 also occurred in the lowermost layers of the overlying keratogenous zone. The Hair matrix Keratin hHb5, but not its type II partner hHa5, was seen in the entire keratogenous zone of the apical and ventral matrix, but was also located in the uppermost cell layers of the basal compartment of the ventral matrix, where it overlapped with K5 and K17. Similar to their sequential expression in the Hair follicle cortex, Hair Keratins hHa1, hHb1, hHb6 and hHa4 were consecutively expressed in the keratogenous zone of both the ventral and, albeit less distinctly, apical matrix, with hHa1 initiating in the lowermost cell layers. The expression of hHa8 in only single cortex cells of the Hair follicle was also preserved in cells of the keratogenous zone. In the region of the so-called dorsal matrix, we observed two histologically and histochemically distinct types of epithelia: (i) a dominant type, histologically similar to the eponychium and an associated K5, K17 and K10 Keratin pattern which clearly extended into the apical matrix, and (ii) a minor type, histologically resembling the postulated dorsal matrix without a granular layer and a cuticle, and exhibiting extended K5 expression as well as Hair Keratin expression in superficial cells. Conclusions The coexpression of hHb5 with K5 and K17 in the uppermost cell layers of the basal compartment and the lowermost layers of the keratogenous zone of the ventral matrix prompts us to designate this region the prekeratogenous zone of the ventral matrix. The two alternating types of histology and Keratin expression in the dorsal matrix identify this region as a transitional zone between the eponychium and the apical matrix. Finally, our data clearly show that the ventral matrix is the main source of the nail plate. In addition, the mixed scenario of Hair and epithelial Keratins, including demonstrable amounts of K10, in superficial cells of the apical matrix, lends support to the notion that the dorsal portion of the nail is generated by the apical matrix.
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Hair Keratin associated proteins characterization of a second high sulfur kap gene domain on human chromosome 21
Journal of Investigative Dermatology, 2004Co-Authors: Michael A. Rogers, Iris Beckmann, Hermelita Winter, Jürgen Schweizer, Lutz Langbein, Silke PraetzelAbstract:Analysis of the EBI/GeneBank database using nonhuman Hair Keratin associated protein (KAP) gene sequences as a query resulted in the identification of two human KAP gene domains on chromosome 21, one of which, located at 21q22.1, has recently been characterized. The second domain presented here, an approximately 90 kb domain on chromosome 21q23, harbored 16 KAP genes and two KAP pseudogenes. By comparison with known sheep and mouse KAP families, these genes could be assigned to two KAP families, KAP10 and KAP12, with the KAP10 family (12 members) being distinctly larger than the KAP12 family (four members). Systematic cDNA/3′ rapid amplification of cDNA ends isolation studies using human scalp mRNA led to the identification of eight KAP10 and two KAP12 cDNA sequences. In situ hybridization analyses of human anagen Hair follicles using specific 3′-noncoding sequences of the various KAP10/KAP12 genes revealed mRNA expression of nearly all KAP10 and KAP12 members exclusively in a narrow region of the middle portion of the Hair fiber cuticle. Bioinformatic analyses of the promoter regions of the KAP10/KAP12 genes demonstrated several enhancer elements that were present in nearly all of the KAP genes. Primary among these were binding elements for the ETS, heat shock factor, AML, and HOX families of transcription factors.
Michael A. Rogers - One of the best experts on this subject based on the ideXlab platform.
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expression patterns of Keratin intermediate filament and Keratin associated protein genes in wool follicles
Differentiation, 2009Co-Authors: Steven W Gordon, Simon C Bawden, Michael A. Rogers, A J Nixon, J E Wildermoth, Nauman J Maqbool, A J PearsonAbstract:The catalogue of Hair Keratin intermediate filaments (KIFs) and Keratin-associated proteins (KAPs) present in wool follicles is incomplete. The full coding sequences for three novel sheep KIFs (KRT27, KRT35 and KRT38) and one KAP (KRTAP4-3) were established in this study. Spatial expression patterns of these and other genes (KRT31, KRT85, KRTAP6-1 and trichohyalin) were determined by in situ hybridisation in wool follicles at synchronised stages of growth. Transcription proceeded in the order: trichohyalin, KRT27, KRT85, KRT35, KRT31, KRT38, KRTAP6-1 and KRTAP4-3, as determined by increasing distance of their expression zones from the germinal matrix in anagen follicles. Expression became gradually more restricted to the lower follicle during follicle regression (catagen), and ceased during dormancy (telogen). Some genes (KRT27, KRT31, KRT85 and KRTAP6-1), but not others, were expressed in cortical cells forming the brush-end, indicating specific requirements for the formation of this anchoring structure. The resumption of Keratin expression was observed only in later stages of follicle reactivation (proanagen). KIF expression patterns in primary wool follicles showed general resemblance to their human homologues but with some unique features. Consistent differences in localisation between primary and secondary wool follicles were observed. Asymmetrical expression of KRT27, KRT31, KRT35, KRT85 and trichohyalin genes in secondary follicles were associated with bulb deflection and follicle curvature, suggesting a role in the determination of follicle and fibre morphology.
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characterization of human kap24 1 a cuticular Hair Keratin associated protein with unusual amino acid composition and repeat structure
Journal of Investigative Dermatology, 2007Co-Authors: Michael A. Rogers, Hermelita Winter, Lutz Langbein, Luis F Javesuarez, Anke Wollschlager, Silke Praetzelwunder, Jürgen SchweizerAbstract:In a search for genes overexpressed in human sexual Hairs, several partial complementary DNA (cDNA) sequences were isolated. Screening of a human scalp cDNA library with one fragment led to the isolation of a full-length cDNA clone, which showed identity to another known sequence, termed KAP24-1 (AB09693). Bioinformatic analysis revealed that the gene for this cDNA consisted of one exon and was located ca. 86 kb away from the chromosome 21q22.1 Keratin-associated protein (KAP) gene domain. RT-PCR analysis of a variety of organs showed that KAP24.1 was only present in human scalp. The KAP24.1 protein consisted of 254 amino acids, exhibited a high content of serine, proline, and tyrosine, but low cysteine content and possessed several carboxyterminal tyrosine-containing tandem decameric repeat structures. Evolutionary tree analysis showed no association to other KAP family members. In situ hybridization and indirect immunofluorescence microscopy studies using an antibody derived from KAP24.1 demonstrated specific expression in the middle/upper Hair cuticle. The structure of the KRTAP24, its proximity to the chromosome 21q22.1 KAP gene domain, the presence of repeat motifs in the protein and its localization in the Hair cuticle points to KAP24.1 being a novel human KAP family member.
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androgen regulation of the human Hair follicle the type i Hair Keratin hha7 is a direct target gene in trichocytes
Journal of Investigative Dermatology, 2004Co-Authors: Luis F Javesuarez, Silke Praetzel, Hermelita Winter, Lutz Langbein, Michael A. Rogers, J SchweizerAbstract:Previous work had shown that most members of the complex human Hair Keratin family were expressed in terminal scalp Hairs. An exception to this rule was the type I Hair Keratin hHa7, which was only detected in some but not all vellus Hairs of the human scalp (Langbein et al , 1999). Here we show that hHa7 exhibits constitutive expression in medullary cells of all types of male and female sexual Hairs. Medullated beard, axillary, and pubic Hairs arise during puberty from small, unmedullated vellus Hairs under the influence of circulating androgens. This suggested an androgen-controlled expression of the hHa7 gene. Further evidence for this assumption was provided by the demonstration of androgen receptor (AR) expression in the nuclei of medullary cells of beard Hairs. Moreover, homology search for the semipalindromic androgen receptor-binding element (ARE) consensus sequence GG A / T ACAnnnTGTTCT in the proximal hHa7 promoter revealed three putative ARE motifs. Electrophoretic mobility shift assays demonstrated the specific binding of AR to all three hHa7 AREs. Their function as AR-responsive elements, either individually or in concert within the hHa7 promoter, could be further confirmed by transfection studies with or without an AR expression vector in PtK2 and prostate PC3-Arwt cells, respectively in the presence or absence of a synthetic androgen. Our study detected hHa7 as the first gene in Hair follicle trichocytes whose expression appears to be directly regulated by androgens. As such, hHa7 represents a marker for androgen action on Hair follicles and might be a suitable tool for investigations of androgen-dependent Hair disorders.
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Hair Keratin associated proteins characterization of a second high sulfur kap gene domain on human chromosome 21
Journal of Investigative Dermatology, 2004Co-Authors: Michael A. Rogers, Iris Beckmann, Hermelita Winter, Jürgen Schweizer, Lutz Langbein, Silke PraetzelAbstract:Analysis of the EBI/GeneBank database using nonhuman Hair Keratin associated protein (KAP) gene sequences as a query resulted in the identification of two human KAP gene domains on chromosome 21, one of which, located at 21q22.1, has recently been characterized. The second domain presented here, an approximately 90 kb domain on chromosome 21q23, harbored 16 KAP genes and two KAP pseudogenes. By comparison with known sheep and mouse KAP families, these genes could be assigned to two KAP families, KAP10 and KAP12, with the KAP10 family (12 members) being distinctly larger than the KAP12 family (four members). Systematic cDNA/3′ rapid amplification of cDNA ends isolation studies using human scalp mRNA led to the identification of eight KAP10 and two KAP12 cDNA sequences. In situ hybridization analyses of human anagen Hair follicles using specific 3′-noncoding sequences of the various KAP10/KAP12 genes revealed mRNA expression of nearly all KAP10 and KAP12 members exclusively in a narrow region of the middle portion of the Hair fiber cuticle. Bioinformatic analyses of the promoter regions of the KAP10/KAP12 genes demonstrated several enhancer elements that were present in nearly all of the KAP genes. Primary among these were binding elements for the ETS, heat shock factor, AML, and HOX families of transcription factors.
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k6irs1 k6irs2 k6irs3 and k6irs4 represent the inner root sheath specific type ii epithelial Keratins of the human Hair follicle1
Journal of Investigative Dermatology, 2003Co-Authors: Lutz Langbein, Silke Praetzel, Hermelita Winter, Michael A. Rogers, Jürgen SchweizerAbstract:In this study we report on the cloning of two novel human type II Keratin cDNAs, K6irs3 and K6irs4, which were specifically expressed in the inner root sheath of the Hair follicle. Together with the genes of two previously described type II inner root sheath Keratins, K6irs1 and K6irs2, the K6irs3 and K6irs4 genes were subclustered in the type II Keratin/Hair Keratin gene domain on chromosome 12q13. Evolutionary tree analysis using all known type II epithelial and Hair Keratins revealed that the K6irs1–4 formed a branch separate from the other epithelial and Hair Keratins. RNA in situ hybridization and indirect immunofluorescence studies of human Hair follicles, which also included the K6irs2 Keratin, demonstrated that both K6irs2 and K6irs3 were specifically expressed in the inner root sheath cuticle, but showed a different onset of expression in this compartment. Whereas the K6irs3 expression began in the lowermost bulb region, that of K6irs2 was delayed up to the height of the apex of the dermal papilla. In contrast, the K6irs4 Keratin was specifically expressed in the Huxley layer. Moreover, K6irs4 was ideally suited to further investigate the occurrence of Flugelzellen, i.e., Huxley cells, characterized by horizontal cell extensions that pass through the Henle layer, abut upon the companion layer, and form desmosomal connections with the surrounding cells. Previously, we detected Flugelzellen only in the region along the differentiated Henle layer. Using the Huxley-cell-specific K6irs4 antiserum, we now demonstrate this cell type to be clearly apposed to the entire Henle layer. We provide evidence that Flugelzellen penetrate the Henle layer actively and may play a role in conferring plasticity and resilience to the otherwise rigid upper Henle layer.
Hermelita Winter - One of the best experts on this subject based on the ideXlab platform.
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characterization of human kap24 1 a cuticular Hair Keratin associated protein with unusual amino acid composition and repeat structure
Journal of Investigative Dermatology, 2007Co-Authors: Michael A. Rogers, Hermelita Winter, Lutz Langbein, Luis F Javesuarez, Anke Wollschlager, Silke Praetzelwunder, Jürgen SchweizerAbstract:In a search for genes overexpressed in human sexual Hairs, several partial complementary DNA (cDNA) sequences were isolated. Screening of a human scalp cDNA library with one fragment led to the isolation of a full-length cDNA clone, which showed identity to another known sequence, termed KAP24-1 (AB09693). Bioinformatic analysis revealed that the gene for this cDNA consisted of one exon and was located ca. 86 kb away from the chromosome 21q22.1 Keratin-associated protein (KAP) gene domain. RT-PCR analysis of a variety of organs showed that KAP24.1 was only present in human scalp. The KAP24.1 protein consisted of 254 amino acids, exhibited a high content of serine, proline, and tyrosine, but low cysteine content and possessed several carboxyterminal tyrosine-containing tandem decameric repeat structures. Evolutionary tree analysis showed no association to other KAP family members. In situ hybridization and indirect immunofluorescence microscopy studies using an antibody derived from KAP24.1 demonstrated specific expression in the middle/upper Hair cuticle. The structure of the KRTAP24, its proximity to the chromosome 21q22.1 KAP gene domain, the presence of repeat motifs in the protein and its localization in the Hair cuticle points to KAP24.1 being a novel human KAP family member.
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androgen regulation of the human Hair follicle the type i Hair Keratin hha7 is a direct target gene in trichocytes
Journal of Investigative Dermatology, 2004Co-Authors: Luis F Javesuarez, Silke Praetzel, Hermelita Winter, Lutz Langbein, Michael A. Rogers, J SchweizerAbstract:Previous work had shown that most members of the complex human Hair Keratin family were expressed in terminal scalp Hairs. An exception to this rule was the type I Hair Keratin hHa7, which was only detected in some but not all vellus Hairs of the human scalp (Langbein et al , 1999). Here we show that hHa7 exhibits constitutive expression in medullary cells of all types of male and female sexual Hairs. Medullated beard, axillary, and pubic Hairs arise during puberty from small, unmedullated vellus Hairs under the influence of circulating androgens. This suggested an androgen-controlled expression of the hHa7 gene. Further evidence for this assumption was provided by the demonstration of androgen receptor (AR) expression in the nuclei of medullary cells of beard Hairs. Moreover, homology search for the semipalindromic androgen receptor-binding element (ARE) consensus sequence GG A / T ACAnnnTGTTCT in the proximal hHa7 promoter revealed three putative ARE motifs. Electrophoretic mobility shift assays demonstrated the specific binding of AR to all three hHa7 AREs. Their function as AR-responsive elements, either individually or in concert within the hHa7 promoter, could be further confirmed by transfection studies with or without an AR expression vector in PtK2 and prostate PC3-Arwt cells, respectively in the presence or absence of a synthetic androgen. Our study detected hHa7 as the first gene in Hair follicle trichocytes whose expression appears to be directly regulated by androgens. As such, hHa7 represents a marker for androgen action on Hair follicles and might be a suitable tool for investigations of androgen-dependent Hair disorders.
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Hair Keratin associated proteins characterization of a second high sulfur kap gene domain on human chromosome 21
Journal of Investigative Dermatology, 2004Co-Authors: Michael A. Rogers, Iris Beckmann, Hermelita Winter, Jürgen Schweizer, Lutz Langbein, Silke PraetzelAbstract:Analysis of the EBI/GeneBank database using nonhuman Hair Keratin associated protein (KAP) gene sequences as a query resulted in the identification of two human KAP gene domains on chromosome 21, one of which, located at 21q22.1, has recently been characterized. The second domain presented here, an approximately 90 kb domain on chromosome 21q23, harbored 16 KAP genes and two KAP pseudogenes. By comparison with known sheep and mouse KAP families, these genes could be assigned to two KAP families, KAP10 and KAP12, with the KAP10 family (12 members) being distinctly larger than the KAP12 family (four members). Systematic cDNA/3′ rapid amplification of cDNA ends isolation studies using human scalp mRNA led to the identification of eight KAP10 and two KAP12 cDNA sequences. In situ hybridization analyses of human anagen Hair follicles using specific 3′-noncoding sequences of the various KAP10/KAP12 genes revealed mRNA expression of nearly all KAP10 and KAP12 members exclusively in a narrow region of the middle portion of the Hair fiber cuticle. Bioinformatic analyses of the promoter regions of the KAP10/KAP12 genes demonstrated several enhancer elements that were present in nearly all of the KAP genes. Primary among these were binding elements for the ETS, heat shock factor, AML, and HOX families of transcription factors.
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k6irs1 k6irs2 k6irs3 and k6irs4 represent the inner root sheath specific type ii epithelial Keratins of the human Hair follicle1
Journal of Investigative Dermatology, 2003Co-Authors: Lutz Langbein, Silke Praetzel, Hermelita Winter, Michael A. Rogers, Jürgen SchweizerAbstract:In this study we report on the cloning of two novel human type II Keratin cDNAs, K6irs3 and K6irs4, which were specifically expressed in the inner root sheath of the Hair follicle. Together with the genes of two previously described type II inner root sheath Keratins, K6irs1 and K6irs2, the K6irs3 and K6irs4 genes were subclustered in the type II Keratin/Hair Keratin gene domain on chromosome 12q13. Evolutionary tree analysis using all known type II epithelial and Hair Keratins revealed that the K6irs1–4 formed a branch separate from the other epithelial and Hair Keratins. RNA in situ hybridization and indirect immunofluorescence studies of human Hair follicles, which also included the K6irs2 Keratin, demonstrated that both K6irs2 and K6irs3 were specifically expressed in the inner root sheath cuticle, but showed a different onset of expression in this compartment. Whereas the K6irs3 expression began in the lowermost bulb region, that of K6irs2 was delayed up to the height of the apex of the dermal papilla. In contrast, the K6irs4 Keratin was specifically expressed in the Huxley layer. Moreover, K6irs4 was ideally suited to further investigate the occurrence of Flugelzellen, i.e., Huxley cells, characterized by horizontal cell extensions that pass through the Henle layer, abut upon the companion layer, and form desmosomal connections with the surrounding cells. Previously, we detected Flugelzellen only in the region along the differentiated Henle layer. Using the Huxley-cell-specific K6irs4 antiserum, we now demonstrate this cell type to be clearly apposed to the entire Henle layer. We provide evidence that Flugelzellen penetrate the Henle layer actively and may play a role in conferring plasticity and resilience to the otherwise rigid upper Henle layer.
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the catalog of human Hair Keratins ii expression of the six type ii members in the Hair follicle and the combined catalog of human type i and ii Keratins
Journal of Biological Chemistry, 2001Co-Authors: Lutz Langbein, Silke Praetzel, Hermelita Winter, Michael A. Rogers, J SchweizerAbstract:Abstract The human type II Hair Keratin subfamily consists of six individual members and can be divided into two groups. The group A members hHb1, hHb3, and hHb6 are structurally related, whereas group C members hHb2, hHb4, and hHb5 are rather distinct. Specific antisera against the individual Hair Keratins were used to establish the two-dimensional catalog of human type II Hair Keratins. In this catalog, hHb5 showed up as a series of isoelectric variants, well separated from a lower, more acidic, and complex protein streak containing isoelectric variants of Hair Keratins hHb1, hHb2, hHb3, and hHb6. Both in situ hybridization and immunohistochemistry on anagen Hair follicles showed that hHb5 and hHb2 defined early stages of Hair differentiation in the matrix (hHb5) and cuticle (hHb5 and hHb2), respectively. Although cuticular differentiation proceeded without the expression of further type II Hair Keratins, cortex cells simultaneously expressed hHb1, hHb3, and hHb6 at an advanced stage of differentiation. In contrast, hHb4, which is undetectable in Hair follicle extracts and sections, could be identified as the largest and most alkaline member of this subfamily in cytoskeletal extracts of dorsal tongue. This Hair Keratin was localized in the posterior compartment of the tongue filiform papillae. Comparative analysis of type II with the previously published type I Hair Keratin expression profiles suggested specific, but more likely, random Keratin-pairing principles during trichocyte differentiation. Finally, by combining the previously published type I Hair Keratin catalog with the type II Hair Keratin catalog and integrating both into the existing catalog of human epithelial Keratins, we present a two-dimensional compilation of the presently known human Keratins.
Lutz Langbein - One of the best experts on this subject based on the ideXlab platform.
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characterization of human kap24 1 a cuticular Hair Keratin associated protein with unusual amino acid composition and repeat structure
Journal of Investigative Dermatology, 2007Co-Authors: Michael A. Rogers, Hermelita Winter, Lutz Langbein, Luis F Javesuarez, Anke Wollschlager, Silke Praetzelwunder, Jürgen SchweizerAbstract:In a search for genes overexpressed in human sexual Hairs, several partial complementary DNA (cDNA) sequences were isolated. Screening of a human scalp cDNA library with one fragment led to the isolation of a full-length cDNA clone, which showed identity to another known sequence, termed KAP24-1 (AB09693). Bioinformatic analysis revealed that the gene for this cDNA consisted of one exon and was located ca. 86 kb away from the chromosome 21q22.1 Keratin-associated protein (KAP) gene domain. RT-PCR analysis of a variety of organs showed that KAP24.1 was only present in human scalp. The KAP24.1 protein consisted of 254 amino acids, exhibited a high content of serine, proline, and tyrosine, but low cysteine content and possessed several carboxyterminal tyrosine-containing tandem decameric repeat structures. Evolutionary tree analysis showed no association to other KAP family members. In situ hybridization and indirect immunofluorescence microscopy studies using an antibody derived from KAP24.1 demonstrated specific expression in the middle/upper Hair cuticle. The structure of the KRTAP24, its proximity to the chromosome 21q22.1 KAP gene domain, the presence of repeat motifs in the protein and its localization in the Hair cuticle points to KAP24.1 being a novel human KAP family member.
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Keratins of the human Hair follicle
International Review of Cytology-a Survey of Cell Biology, 2005Co-Authors: Lutz Langbein, Jürgen SchweizerAbstract:Abstract Substantial progress has been made regarding the elucidation of differentiation processes of the human Hair follicle. This review first describes the genomic organization of the human Hair Keratin gene family and the complex expression characteristics of Hair Keratins in the Hair-forming compartment. Sections describe the role and fate of Hair Keratins in the diseased Hair follicle, particularly hereditary disorders and Hair follicle–derived tumors. Also included is a report on the actual state of knowledge concerning the regulation of Hair Keratin expression. In the second part of this review, essentially the same principles are applied to outline more recent and, thus, occasionally fewer data on specialized epithelial Keratins expressed in various tissue constituents of the external sheaths and the companion layer of the follicle. A closing outlook highlights issues that need to be explored further to deepen our insight into the biology and genetics of the Hair follicle.
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expression of Hair Keratins in the adult nail unit an immunohistochemical analysis of the onychogenesis in the proximal nail fold matrix and nail bed
British Journal of Dermatology, 2004Co-Authors: Christophe Perrin, Lutz Langbein, Jürgen SchweizerAbstract:Summary Background Recently, the expression profiles of the members of the complex Hair Keratin family have been determined in the human anagen Hair follicle. In contrast, the details of Hair Keratin expression in the human nail unit are poorly known. Objectives In order to fill this gap, we have performed an immunohistochemical study of the adult human nail unit by means of specific antibodies against nine Hair Keratins of both types (hHa2, hHb2, hHa5, hHb5, hHa1, hHb1, hHb6, hHa4 and hHa8) as well as three epithelial Keratins (K5, K17 and K10). Methods Formalin-fixed paraffin sections of adult nails were examined using monoclonal and polyclonal Keratin antibodies, respectively. Longitudinal as well as transverse sections were investigated. Results Our study revealed two types of epithelial tissue compartments in the nail unit. The first comprised the eponychium and hyponychium and the nail bed, which expressed only epithelial Keratins. While Keratins K5, K17 (basal) and K10 (suprabasal) were found in the orthoKeratinizing eponychium and hyponychium, throughout, the nail bed epithelium expressed only K5 and K17. The second type comprised the apical and ventral matrix which exhibited a mixed pattern of epithelial and Hair Keratin expression. Thus, K5 and K17 were expressed in the entire multilayered basal cell compartment of the apical and ventral matrix; however, in the latter, K5 and K17 also occurred in the lowermost layers of the overlying keratogenous zone. The Hair matrix Keratin hHb5, but not its type II partner hHa5, was seen in the entire keratogenous zone of the apical and ventral matrix, but was also located in the uppermost cell layers of the basal compartment of the ventral matrix, where it overlapped with K5 and K17. Similar to their sequential expression in the Hair follicle cortex, Hair Keratins hHa1, hHb1, hHb6 and hHa4 were consecutively expressed in the keratogenous zone of both the ventral and, albeit less distinctly, apical matrix, with hHa1 initiating in the lowermost cell layers. The expression of hHa8 in only single cortex cells of the Hair follicle was also preserved in cells of the keratogenous zone. In the region of the so-called dorsal matrix, we observed two histologically and histochemically distinct types of epithelia: (i) a dominant type, histologically similar to the eponychium and an associated K5, K17 and K10 Keratin pattern which clearly extended into the apical matrix, and (ii) a minor type, histologically resembling the postulated dorsal matrix without a granular layer and a cuticle, and exhibiting extended K5 expression as well as Hair Keratin expression in superficial cells. Conclusions The coexpression of hHb5 with K5 and K17 in the uppermost cell layers of the basal compartment and the lowermost layers of the keratogenous zone of the ventral matrix prompts us to designate this region the prekeratogenous zone of the ventral matrix. The two alternating types of histology and Keratin expression in the dorsal matrix identify this region as a transitional zone between the eponychium and the apical matrix. Finally, our data clearly show that the ventral matrix is the main source of the nail plate. In addition, the mixed scenario of Hair and epithelial Keratins, including demonstrable amounts of K10, in superficial cells of the apical matrix, lends support to the notion that the dorsal portion of the nail is generated by the apical matrix.
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androgen regulation of the human Hair follicle the type i Hair Keratin hha7 is a direct target gene in trichocytes
Journal of Investigative Dermatology, 2004Co-Authors: Luis F Javesuarez, Silke Praetzel, Hermelita Winter, Lutz Langbein, Michael A. Rogers, J SchweizerAbstract:Previous work had shown that most members of the complex human Hair Keratin family were expressed in terminal scalp Hairs. An exception to this rule was the type I Hair Keratin hHa7, which was only detected in some but not all vellus Hairs of the human scalp (Langbein et al , 1999). Here we show that hHa7 exhibits constitutive expression in medullary cells of all types of male and female sexual Hairs. Medullated beard, axillary, and pubic Hairs arise during puberty from small, unmedullated vellus Hairs under the influence of circulating androgens. This suggested an androgen-controlled expression of the hHa7 gene. Further evidence for this assumption was provided by the demonstration of androgen receptor (AR) expression in the nuclei of medullary cells of beard Hairs. Moreover, homology search for the semipalindromic androgen receptor-binding element (ARE) consensus sequence GG A / T ACAnnnTGTTCT in the proximal hHa7 promoter revealed three putative ARE motifs. Electrophoretic mobility shift assays demonstrated the specific binding of AR to all three hHa7 AREs. Their function as AR-responsive elements, either individually or in concert within the hHa7 promoter, could be further confirmed by transfection studies with or without an AR expression vector in PtK2 and prostate PC3-Arwt cells, respectively in the presence or absence of a synthetic androgen. Our study detected hHa7 as the first gene in Hair follicle trichocytes whose expression appears to be directly regulated by androgens. As such, hHa7 represents a marker for androgen action on Hair follicles and might be a suitable tool for investigations of androgen-dependent Hair disorders.
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Hair Keratin associated proteins characterization of a second high sulfur kap gene domain on human chromosome 21
Journal of Investigative Dermatology, 2004Co-Authors: Michael A. Rogers, Iris Beckmann, Hermelita Winter, Jürgen Schweizer, Lutz Langbein, Silke PraetzelAbstract:Analysis of the EBI/GeneBank database using nonhuman Hair Keratin associated protein (KAP) gene sequences as a query resulted in the identification of two human KAP gene domains on chromosome 21, one of which, located at 21q22.1, has recently been characterized. The second domain presented here, an approximately 90 kb domain on chromosome 21q23, harbored 16 KAP genes and two KAP pseudogenes. By comparison with known sheep and mouse KAP families, these genes could be assigned to two KAP families, KAP10 and KAP12, with the KAP10 family (12 members) being distinctly larger than the KAP12 family (four members). Systematic cDNA/3′ rapid amplification of cDNA ends isolation studies using human scalp mRNA led to the identification of eight KAP10 and two KAP12 cDNA sequences. In situ hybridization analyses of human anagen Hair follicles using specific 3′-noncoding sequences of the various KAP10/KAP12 genes revealed mRNA expression of nearly all KAP10 and KAP12 members exclusively in a narrow region of the middle portion of the Hair fiber cuticle. Bioinformatic analyses of the promoter regions of the KAP10/KAP12 genes demonstrated several enhancer elements that were present in nearly all of the KAP genes. Primary among these were binding elements for the ETS, heat shock factor, AML, and HOX families of transcription factors.
J Schweizer - One of the best experts on this subject based on the ideXlab platform.
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androgen regulation of the human Hair follicle the type i Hair Keratin hha7 is a direct target gene in trichocytes
Journal of Investigative Dermatology, 2004Co-Authors: Luis F Javesuarez, Silke Praetzel, Hermelita Winter, Lutz Langbein, Michael A. Rogers, J SchweizerAbstract:Previous work had shown that most members of the complex human Hair Keratin family were expressed in terminal scalp Hairs. An exception to this rule was the type I Hair Keratin hHa7, which was only detected in some but not all vellus Hairs of the human scalp (Langbein et al , 1999). Here we show that hHa7 exhibits constitutive expression in medullary cells of all types of male and female sexual Hairs. Medullated beard, axillary, and pubic Hairs arise during puberty from small, unmedullated vellus Hairs under the influence of circulating androgens. This suggested an androgen-controlled expression of the hHa7 gene. Further evidence for this assumption was provided by the demonstration of androgen receptor (AR) expression in the nuclei of medullary cells of beard Hairs. Moreover, homology search for the semipalindromic androgen receptor-binding element (ARE) consensus sequence GG A / T ACAnnnTGTTCT in the proximal hHa7 promoter revealed three putative ARE motifs. Electrophoretic mobility shift assays demonstrated the specific binding of AR to all three hHa7 AREs. Their function as AR-responsive elements, either individually or in concert within the hHa7 promoter, could be further confirmed by transfection studies with or without an AR expression vector in PtK2 and prostate PC3-Arwt cells, respectively in the presence or absence of a synthetic androgen. Our study detected hHa7 as the first gene in Hair follicle trichocytes whose expression appears to be directly regulated by androgens. As such, hHa7 represents a marker for androgen action on Hair follicles and might be a suitable tool for investigations of androgen-dependent Hair disorders.
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Hair Keratin pattern in human Hair follicles grown in vitro
Experimental Dermatology, 2003Co-Authors: Sebastien Thibaut, C Collin, L Langbein, J Schweizer, Brigitte Gautier, Bruno BernardAbstract:Abstract: The Keratin family includes epithelial (soft) Keratins and Hair (hard) Keratins, and can be divided into acidic type I and basic to neutral type II subfamilies. Recently, nine type I and six type II Hair Keratin genes have been characterized through the screening of a human PAC library. The expression of these genes in the Hair follicle was determined in vivo and a combined catalog of acidic and basic Hair Keratins was established. In this study, we investigated the expression and localization of most of the human Hair Keratin members of both types in human Hair grown in vitro. We show that in vitro growth of Hair follicles for 10 days in complete William's E culture medium did not alter the expression pattern of Hair Keratins. Similarly to the in vivo situation, each Hair Keratin was localized in precise and discrete compartments of the follicle, ranging from the matrix to the upper cortex and/or the Hair cuticle. This study shows that the increase in length of in vitro grown follicles was accompanied by the proper Hair shaft Keratinization process. It also shows that Hair follicle integrity was maintained in vitro, both in terms of gross morphology and molecular organization despite the complexity of the Keratin expression pattern.
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the catalog of human Hair Keratins ii expression of the six type ii members in the Hair follicle and the combined catalog of human type i and ii Keratins
Journal of Biological Chemistry, 2001Co-Authors: Lutz Langbein, Silke Praetzel, Hermelita Winter, Michael A. Rogers, J SchweizerAbstract:Abstract The human type II Hair Keratin subfamily consists of six individual members and can be divided into two groups. The group A members hHb1, hHb3, and hHb6 are structurally related, whereas group C members hHb2, hHb4, and hHb5 are rather distinct. Specific antisera against the individual Hair Keratins were used to establish the two-dimensional catalog of human type II Hair Keratins. In this catalog, hHb5 showed up as a series of isoelectric variants, well separated from a lower, more acidic, and complex protein streak containing isoelectric variants of Hair Keratins hHb1, hHb2, hHb3, and hHb6. Both in situ hybridization and immunohistochemistry on anagen Hair follicles showed that hHb5 and hHb2 defined early stages of Hair differentiation in the matrix (hHb5) and cuticle (hHb5 and hHb2), respectively. Although cuticular differentiation proceeded without the expression of further type II Hair Keratins, cortex cells simultaneously expressed hHb1, hHb3, and hHb6 at an advanced stage of differentiation. In contrast, hHb4, which is undetectable in Hair follicle extracts and sections, could be identified as the largest and most alkaline member of this subfamily in cytoskeletal extracts of dorsal tongue. This Hair Keratin was localized in the posterior compartment of the tongue filiform papillae. Comparative analysis of type II with the previously published type I Hair Keratin expression profiles suggested specific, but more likely, random Keratin-pairing principles during trichocyte differentiation. Finally, by combining the previously published type I Hair Keratin catalog with the type II Hair Keratin catalog and integrating both into the existing catalog of human epithelial Keratins, we present a two-dimensional compilation of the presently known human Keratins.
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a cdna encoding the human type i Hair Keratin hha1
Biochimica et Biophysica Acta, 1995Co-Authors: P Fink, Hermelita Winter, Michael A. Rogers, Bernhard P Korge, J SchweizerAbstract:Abstract A full-length cDNA of a human type I Hair Keratin was isolated that encodes a protein of 416 amino acids. Northern blot analysis shows that the mRNA is present in human scalp but not in Hairless skin. Based on sequence homology comparisons with the four known mouse type I Hair Keratins mHa1–4 the Keratin could be identified as the human Hair Keratin hHa1.
