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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 new members of the human Type II Keratin gene family and a general evaluation of the Keratin gene domain on chromosome 12q13 13
Journal of Investigative Dermatology, 2005Co-Authors: Michael A. Rogers, Hermelita Winter, Lutz Langbein, Lutz Edler, Iris Beckmann, Jürgen SchweizerAbstract:The recent completion of a reference sequence of the human genome now allows a complete characterization of the Type II Keratin gene domain on chromosome 12q13.13. This, domain, approximately 780 kb in size, is present on nine bacterial artificial chromosome clones sequenced by the Human Genome Sequencing Project. The Type II Keratin domain contains 27 Keratin genes and eight pseudogenes. Twenty-three of these genes and four pseudogenes have been previously reported. This study describes, in addition to the genomic sequencing of the K2p gene and the bioinformatic identification of four Keratin pseudogenes, the characterization of cDNA corresponding to three previously undescribed Keratin genes K1b, K6l, and Kb20, as well as cDNA sequences for the previously described Keratin genes hHb2, hHb4, and K3. Northern analysis of the new Keratins K1b, K6l, K5b, and Kb20 using mRNA of major organs as well as of specific epithelial subTypes shows singular expression of these Keratins in skin, hair follicles and, for K5b and Kb20, in tongue, respectively. In addition, the obvious discrepancies between the current reference sequence of the human genome and the previously described gene/cDNA sequences for K6c, K6d, K6e, K6f, K6h are investigated, leading to the conclusion that K6c, K6d as well as K6e, K6f are probably polymorphic variants of K6a and K6h, respectively. All 26 human Type II Keratins found on this domain as well as K18, dType 1 Keratin, are identified at the genomic and transcriptional level. This appears to be the total complement of functional Type II Keratins in humans.
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the human Type i Keratin gene family characterization of new hair follicle specific members and evaluation of the chromosome 17q21 2 gene domain
Differentiation, 2004Co-Authors: Michael A. Rogers, Raphael Bleiler, Hermelita Winter, Lutz Langbein, Jürgen SchweizerAbstract:Abstract In general concurrence with recent studies, bioinformatic analysis of the chromosome 17q21.2 DNA sequence found in the EBI/Genebank database shows the presence of 27 Type I Keratin genes and five Keratin pseudogenes present on 8 contiguous Bacterial Artificial Chromosome (BAC) sequences. This constitutes the 970 kb Type I Keratin gene domain. Inserted into this domain is a 350 kb region harboring 32 previously characterized Keratin-associated protein genes. Of the 27 Keratin genes found in this region, six have not been characterized in detail. This study reports the isolation of cDNA sequences for these Keratin genes, termed K25irs1-K25irs4, Ka35, and Ka36, as well as cDNA sequences for the previously reported hair Keratins hHa3-I, hHa7, and hHa8. RT-PCR analysis of 14 epithelial tissues using primers for the six novel Keratins, as well as for Keratins 23 and 24, shows that the six novel Keratins appear to be hair follicle associated. Previous expression data, coupled with evolutionary analysis studies point to K25irs1–K25irs4 probably being inner root sheath specific Keratins. Ka35 and Ka36 are, based on their exon–intron structure and expression characteristics, hair Keratins. In contrast, K23 and K24 appear to be epithelial Keratins associated with simple/glandular or stratified, non-cornified epithelia, respectively. A literature analysis coupled with the data presented here confirms that all of the 27 Keratin genes found on this domain have been characterized at the transcriptional level. Together with K18, a Type I Keratin gene found on the Type II Keratin domain, this seems to be the entire complement of functional Type I Keratins in humans.
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Type II epithelial Keratin 6hf k6hf is expressed in the companion layer matrix and medulla in anagen stage hair follicles
Journal of Investigative Dermatology, 2003Co-Authors: Zhiling Wang, Jürgen Schweizer, Lutz Langbein, Pauline Wong, Pierre A. CoulombeAbstract:More than half of the known Keratin genes ( n ≈50) are expressed in the hair follicle. An in-depth knowledge of their differential expression in this organ will help us to understand the mechanisms of its formation and cycling, and the etiology of inherited hair disorders. Keratin 6hf is a Type II Keratin recently shown to occur in the companion layer. We cloned the mouse ortholog and characterized its expression in skin and oral mucosa. The mK6hf gene is 9.1 kb long and located in the cluster of Type II Keratin genes on mouse chromosome 15, between the Keratin 6 ( mK6α / mK6β ) and hair Keratin genes. In situ hybridization and protein immunolocalization showed that, in addition to the companion layer, mK6hf is expressed in the upper matrix and medulla of the anagen-stage hair. This distribution is seen for all Types of mouse hairs and medullated human hairs. The distribution of Keratin 6hf protein in the hair shaft mirrors that of Keratin 17, and the observation of reduced levels of Keratin 6hf in Keratin 17 null hair argues for a direct interaction between them. mK6hf is also expressed in the nail bed epithelium and fungiform papillae of dorsal tongue epithelium. Our findings provide an additional marker for the hair matrix and medulla, and suggest that the cellular precursors for the medulla, cortex, and cuticle compartments are already spatially segregated within the hair matrix. They also have obvious implications for the epithelial alterations associated with defects in Keratin 6 genes.
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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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a new mutation in the Type II hair cortex Keratin hhb1 involved in the inherited hair disorder monilethrix
Human Genetics, 1997Co-Authors: Hermelita Winter, Michael A. Rogers, Howard P. Stevens, Mathias Gebhardt, Uwe Wollina, Lionell Boxall, David Chitayat, Riyana Babulhirji, Abreham Zlotogorski, Jürgen SchweizerAbstract:Monilethrix is a rare dominant hair disease characterized by beaded or moniliform hair which results from the periodic thinning of the hair shaft and shows a high propensity to excess weathering and fracturing. Several cases of monilethrix have been linked to the Type II Keratin gene cluster on chromosome 12q13 and causative heterozygous mutations of a highly conserved glutamic acid residue (Glu 410 Lys and Glu 410 Asp) in the helix termination motif of the Type II hair Keratin hHb6 have recently been identified in monilethrix patients of two unrelated families. In the present study, we have investigated two further unrelated monilethrix families as well as a single case. Affected members of one family and the single patient exhibited the prevalent hHb6 Glu 410 Lys mutation. In the second family, we identified in affected individuals a lysine substitution of the corresponding glutamic acid residue, Glu 403, in the Type II hair Keratin hHb1, suggesting that this site represents a mutational hotspot in these highly related Type II hair Keratins. Both hHb1 and hHb6 are largely coexpressed in cortical trichocytes of the hair shaft. This indicates that monilethrix is a disease of the hair cortex.
Ahmad Waseem - One of the best experts on this subject based on the ideXlab platform.
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Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16
Nature Communications, 2017Co-Authors: T Maruthappu, Anissa Chikh, Paul J. Delaney, Clemence Levet, Diana C. Blaydon, Matthew A. Brooke, B Fell, Angela Moncada-pazos, Akemi Ishida-yamamoto, Ahmad WaseemAbstract:Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2−/− mice compared with irhom2+/+mice, due to reduced Keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its Type II Keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this ‘stress’ Keratin is regulated. Keratin 16 is an epithelial protein highly expressed at pressure bearing sites and during wound healing and cancer. Here the authors show that K16 interacts with the inactive protease Rhbdf2, associated with Tylosis with oesophageal cancer, and that this interaction drives increased Keratinocyte proliferation.
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rhomboid family member 2 regulates cytoskeletal stress associated Keratin 16
Nature Communications, 2017Co-Authors: T Maruthappu, Anissa Chikh, Paul J. Delaney, Clemence Levet, Diana C. Blaydon, Matthew A. Brooke, B Fell, Angela Moncadapazos, Akemi Ishidayamamoto, Ahmad WaseemAbstract:Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced Keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its Type II Keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' Keratin is regulated.
Pierre A. Coulombe - One of the best experts on this subject based on the ideXlab platform.
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Directed Expression of a Chimeric Type II Keratin Partially Rescues Keratin 5 Null Mice
The Journal of biological chemistry, 2014Co-Authors: David M. Alvarado, Pierre A. CoulombeAbstract:The crucial role of structural support fulfilled by Keratin intermediate filaments (IFs) in surface epithelia likely requires that they be organized into cross-linked networks. For IFs comprised of Keratins 5 and 14 (K5 and K14), which occur in basal Keratinocytes of the epidermis, formation of cross-linked bundles is, in part, self-driven through cis-acting determinants. Here, we targeted the expression of a bundling-competent KRT5/KRT8 chimeric cDNA (KRT8bc) or bundling-deficient wild Type KRT8 as a control to the epidermal basal layer of Krt5-null mice to assess the functional importance of Keratin IF self-organization in vivo. Such targeted expression of K8bc rescued Krt5-null mice with a 47% frequency, whereas K8 completely failed to do so. This outcome correlated with lower than expected levels of K8bc and especially K8 mRNA and protein in the epidermis of E18.5 replacement embryos. Ex vivo culture of embryonic skin Keratinocytes confirmed the ability of K8bc to form IFs in the absence of K5. Additionally, electron microscopy analysis of E18.5 embryonic skin revealed that the striking defects observed in Keratin IF bundling, cytoarchitecture, and mitochondria are partially restored by K8bc expression. As young adults, viable KRT8bc replacement mice develop alopecia and chronic skin lesions, indicating that the skin epithelia are not completely normal. These findings are consistent with a contribution of self-mediated organization of Keratin IFs to structural support and cytoarchitecture in basal layer Keratinocytes of the epidermis and underscore the importance of context-dependent regulation for Keratin genes and proteins in vivo.
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self organization of Keratin intermediate filaments into cross linked networks
Journal of Cell Biology, 2009Co-Authors: Chang Hun Lee, Pierre A. CoulombeAbstract:Keratins, the largest subgroup of intermediate filament (IF) proteins, form a network of 10-nm filaments built from Type I/II heterodimers in epithelial cells. A major function of Keratin IFs is to protect epithelial cells from mechanical stress. Like filamentous actin, Keratin IFs must be cross-linked in vitro to achieve the high level of mechanical resilience characteristic of live cells. Keratins 5 and 14 (K5 and K14), the main pairing occurring in the basal progenitor layer of epidermis and related epithelia, can readily self-organize into large filament bundles in vitro and in vivo. Here, we show that filament self-organization is mediated by multivalent interactions involving distinct regions in K5 and K14 proteins. Self-organization is determined independently of polymerization into 10-nm filaments, but involves specific Type I–Type II Keratin complementarity. We propose that self-organization is a key determinant of the structural support function of Keratin IFs in vivo.
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Defining the properties of the nonhelical tail domain in Type II Keratin 5: insight from a bullous disease-causing mutation.
Molecular biology of the cell, 2005Co-Authors: Pierre A. CoulombeAbstract:Inherited mutations in the intermediate filament (IF) proteins Keratin 5 (K5) or Keratin 14 (K14) cause epidermolysis bullosa simplex (EBS), in which basal layer Keratinocytes rupture upon trauma to the epidermis. Most mutations are missense alleles affecting amino acids located in the central alpha-helical rod domain of K5 and K14. Here, we study the properties of an unusual EBS-causing mutation in which a nucleotide deletion (1649delG) alters the last 41 amino acids and adds 35 residues to the C terminus of K5. Relative to wild Type, filaments coassembled in vitro from purified K5-1649delG and K14 proteins are shorter and exhibit weak viscoelastic properties when placed under strain. Loss of the C-terminal 41 residues contributes to these alterations. When transfected in cultured epithelial cells, K5-1649delG incorporates into preexisting Keratin IFs and also forms multiple small aggregates that often colocalize with hsp70 in the cytoplasm. Aggregation is purely a function of the K5-1649delG tail domain; in contrast, the cloned 109 residue-long tail domain from wild Type K5 is distributed throughout the cytoplasm and colocalizes partly with Keratin IFs. These data provide a mechanistic basis for the cell fragility seen in individuals bearing the K5-1649delG allele, and point to the role of the C-terminal 41 residues in determining K5's assembly properties.
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great promises yet to be fulfilled defining Keratin intermediate filament function in vivo
European Journal of Cell Biology, 2004Co-Authors: Pierre A. Coulombe, Zhiling Wang, Xuemei Tong, Stacy Mazzalupo, Pauline WongAbstract:Summary Keratins are abundant proteins in epithelial cells, in which they occur as a cytoplasmic network of 10 – 12 nm wide intermediate filaments (IFs). They are encoded by a large family of conserved genes in mammals, with more than 50 individual members partitioned into two sequence Types. A strict requirement for the heteropolymerization of Type I and Type II Keratin proteins during filament formation underlies the pairwise transcriptional regulation of Keratin genes. In addition, individual pairs are regulated in a tissue-Type and differentiation-specific manner. Elucidating the rationale behind the diversity and differential distribution of Keratin proteins offers the promise of novel insight into epithelial biology. At present, we know that Keratin IFs act as resilient yet pliable scaffolds that endow epithelial cells with the ability to sustain mechanical and non-mechanical stresses. Accordingly, inherited mutations altering the coding sequence of Keratins underlie several epithelial fragility disorders. In addition, Keratin IFs influence the cellular response to pro-apoptotic signals in specific settings, and the routing of membrane proteins in polarized epithelia. Here we review studies focused on a subset of Keratin genes, K6, K16 and K17, showing a complex regulation in vivo, including a widely known upregulation during wound repair and in diseased skin. Progress in defining the function of these and other Keratins through gene manipulation in mice has been hampered by functional redundancy within the family. Still, detailed studies of the phenoType exhibited by K6 and K17 null mice yielded novel insight into the properties and function of Keratin IFs in vivo.
Robinaj Eady - One of the best experts on this subject based on the ideXlab platform.
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Genomic organization and amplification of the human epidermal Type II Keratin genes K1 and K5
Biochemical and biophysical research communications, 2000Co-Authors: Neilv Whittock, Robinaj EadyAbstract:Abstract Keratins are a family of structurally related proteins that form the intermediate filament cytoskeleton in epithelial cells. Mutations in K1 and K5 result in the autosomal dominant disorders epidermolytic hyperkeratosis/bullous congenital ichthyosiform erythroderma and epidermolysis bullosa simplex, respectively. Most disease-associated mutations are within exons encoding protein domains involved in Keratin filament assembly. However, some mutations occur outside the mutation hot-spots and may perturb intermolecular interactions between Keratins and other proteins, usually with milder clinical consequences. To screen the entire Keratin 1 and Keratin 5 genes we have characterized their intron–exon organization. The Keratin 1 gene comprises 9 exons spanning approximately 5.6 kb on 12q, and the Keratin 5 gene comprises 9 exons spanning approximately 6.1 kb on 12q. We have also developed a comprehensive PCR-based mutation detection strategy using primers placed on flanking introns followed by direct sequencing of the PCR products.
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mutations in the rod 1a domain of Keratins 1 and 10 in bullous congenital ichthyosiform erythroderma bcie
Journal of Investigative Dermatology, 1994Co-Authors: W Irwin H Mclean, I M Leigh, Robinaj Eady, Patriciajc Doppinghepenstal, Caroline Higgins, James R Mcmillan, Harshad Navsaria, J I Harper, D Paige, S.m. MorleyAbstract:Bullous congenital ichthyosiform erythroderma is a human hereditary skin disorder in which suprabasal Keratinocytes rupture. Recent reports have implicated Keratins K1 and K10 in this disease. Here we describe four diverse Keratin mutations that are all significantly associated with this disease. Two of these are in the helix 1A subdomain of the Type II Keratin 1, giving a serine-to-proline substitution in codon 185 and an asparagine-to-serine substitution in codon 187. In the analogous region of Type I Keratin 10, an arginine-to-proline and an arginine-to-serine transition in codon 156 have been identified. All four mutations create restriction fragment length polymorphisms that were used exclude the mutations from 120 normal chromosomes. Insertional polymorphism (in the V2 subdomains of the non-helical tails of K1 and K10) was excluded as the cause of the phenotypic heterogeneity observed within one family.
Hermelita Winter - One of the best experts on this subject based on the ideXlab platform.
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characterization of new members of the human Type II Keratin gene family and a general evaluation of the Keratin gene domain on chromosome 12q13 13
Journal of Investigative Dermatology, 2005Co-Authors: Michael A. Rogers, Hermelita Winter, Lutz Langbein, Lutz Edler, Iris Beckmann, Jürgen SchweizerAbstract:The recent completion of a reference sequence of the human genome now allows a complete characterization of the Type II Keratin gene domain on chromosome 12q13.13. This, domain, approximately 780 kb in size, is present on nine bacterial artificial chromosome clones sequenced by the Human Genome Sequencing Project. The Type II Keratin domain contains 27 Keratin genes and eight pseudogenes. Twenty-three of these genes and four pseudogenes have been previously reported. This study describes, in addition to the genomic sequencing of the K2p gene and the bioinformatic identification of four Keratin pseudogenes, the characterization of cDNA corresponding to three previously undescribed Keratin genes K1b, K6l, and Kb20, as well as cDNA sequences for the previously described Keratin genes hHb2, hHb4, and K3. Northern analysis of the new Keratins K1b, K6l, K5b, and Kb20 using mRNA of major organs as well as of specific epithelial subTypes shows singular expression of these Keratins in skin, hair follicles and, for K5b and Kb20, in tongue, respectively. In addition, the obvious discrepancies between the current reference sequence of the human genome and the previously described gene/cDNA sequences for K6c, K6d, K6e, K6f, K6h are investigated, leading to the conclusion that K6c, K6d as well as K6e, K6f are probably polymorphic variants of K6a and K6h, respectively. All 26 human Type II Keratins found on this domain as well as K18, dType 1 Keratin, are identified at the genomic and transcriptional level. This appears to be the total complement of functional Type II Keratins in humans.
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the human Type i Keratin gene family characterization of new hair follicle specific members and evaluation of the chromosome 17q21 2 gene domain
Differentiation, 2004Co-Authors: Michael A. Rogers, Raphael Bleiler, Hermelita Winter, Lutz Langbein, Jürgen SchweizerAbstract:Abstract In general concurrence with recent studies, bioinformatic analysis of the chromosome 17q21.2 DNA sequence found in the EBI/Genebank database shows the presence of 27 Type I Keratin genes and five Keratin pseudogenes present on 8 contiguous Bacterial Artificial Chromosome (BAC) sequences. This constitutes the 970 kb Type I Keratin gene domain. Inserted into this domain is a 350 kb region harboring 32 previously characterized Keratin-associated protein genes. Of the 27 Keratin genes found in this region, six have not been characterized in detail. This study reports the isolation of cDNA sequences for these Keratin genes, termed K25irs1-K25irs4, Ka35, and Ka36, as well as cDNA sequences for the previously reported hair Keratins hHa3-I, hHa7, and hHa8. RT-PCR analysis of 14 epithelial tissues using primers for the six novel Keratins, as well as for Keratins 23 and 24, shows that the six novel Keratins appear to be hair follicle associated. Previous expression data, coupled with evolutionary analysis studies point to K25irs1–K25irs4 probably being inner root sheath specific Keratins. Ka35 and Ka36 are, based on their exon–intron structure and expression characteristics, hair Keratins. In contrast, K23 and K24 appear to be epithelial Keratins associated with simple/glandular or stratified, non-cornified epithelia, respectively. A literature analysis coupled with the data presented here confirms that all of the 27 Keratin genes found on this domain have been characterized at the transcriptional level. Together with K18, a Type I Keratin gene found on the Type II Keratin domain, this seems to be the entire complement of functional Type I Keratins in humans.
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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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a new mutation in the Type II hair cortex Keratin hhb1 involved in the inherited hair disorder monilethrix
Human Genetics, 1997Co-Authors: Hermelita Winter, Michael A. Rogers, Howard P. Stevens, Mathias Gebhardt, Uwe Wollina, Lionell Boxall, David Chitayat, Riyana Babulhirji, Abreham Zlotogorski, Jürgen SchweizerAbstract:Monilethrix is a rare dominant hair disease characterized by beaded or moniliform hair which results from the periodic thinning of the hair shaft and shows a high propensity to excess weathering and fracturing. Several cases of monilethrix have been linked to the Type II Keratin gene cluster on chromosome 12q13 and causative heterozygous mutations of a highly conserved glutamic acid residue (Glu 410 Lys and Glu 410 Asp) in the helix termination motif of the Type II hair Keratin hHb6 have recently been identified in monilethrix patients of two unrelated families. In the present study, we have investigated two further unrelated monilethrix families as well as a single case. Affected members of one family and the single patient exhibited the prevalent hHb6 Glu 410 Lys mutation. In the second family, we identified in affected individuals a lysine substitution of the corresponding glutamic acid residue, Glu 403, in the Type II hair Keratin hHb1, suggesting that this site represents a mutational hotspot in these highly related Type II hair Keratins. Both hHb1 and hHb6 are largely coexpressed in cortical trichocytes of the hair shaft. This indicates that monilethrix is a disease of the hair cortex.
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structure and site of expression of a murine Type II hair Keratin
Molecular Biology Reports, 1992Co-Authors: Edda Tobiasch, Jtirgen Schweizer, Hermelita WinterAbstract:We present here a 1770 bp-long cDNA which encodes a murine Type II Keratin. Sequence comparisons of the Keratin with those of various Type II Keratins expressed in mouse epidermis and internal stratified epithelia reveal that the new Keratin is unrelated to epithelial Keratins. Rather the structural organization of its amino- and carboxyterminal domains and the high content of cysteine and proline residues in these regions suggest that the Keratin represents a murine Type II hair Keratin. This assumption was confirmed by in situ hybridization which localized the mRNA of the Keratin in upper cells of the hair cortex and in suprabasal cells of the central core unit of filiform papillae of the tongue. Hybrid selection analyses revealed that the Keratin has a molecular weight of 58 kD. It remains to be seen whether the Keratin corresponds to MHb 3 or MHb 4.
