Structure, Function, and Dynamics of Keratin Intermediate Filaments

Steinert, Peter M.

doi:10.1111/1523-1747.ep12475665

Cited by 182 publications

(111 citation statements)

References 55 publications

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“…38 These observations indicate that the head of type II keratins, but not of type I keratins (which do not possess a H1 region), is crucial for keratin filament formation. 7,39 Furthermore, the two first heptad repeats of the 1A domain of K5 are located at the highly conserved amino terminal rod end of the molecule, spanning the LNNKFASFIDK sequence known as the helix initiation peptide (HIP). It is notable that the three other mutations described in the 1A domain of K5 in EBS-DM (L174F, N176S and F179S) [14][15] and all 16 K14 mutations reported in EBS-DM have been identified within the HIP sequence of these genes.…”

Section: Consequences Of Abnormal Splicing Of Exonmentioning

confidence: 99%

“…However, according to the current model for keratin molecule assembly, the absence of H1 and 1A end sequences from K5 is expected to alter both head-to-tail alignment of dimers, whose rod ends have been suggested to overlap slightly during protofilament formation, and lateral association of staggered K5-K14 dimers at the protofilament and protofibril level. 39,43 Interestingly, despite the fact that keratin aggregates could be seen in basal keratinocytes of skin biopsies from patient II-4, immunofluorescence staining of cultured keratinocytes from the same patient with antibodies BL18 and 14,15 is underlined.…”

Section: Proposed Mechanism Of Diseasementioning

confidence: 99%

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Donor splice site mutation in keratin 5 causes in-frame removal of 22 amino acids of H1 and 1A rod domains in Dowling-Meara epidermolysis bullosa simplex

Rugg

Rochat

et al. 1999

Eur J Hum Genet

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Epidermolysis bullosa simplex (EBS) arises from mutations within the keratin 5 and 14 (K5 and K14) genes which alter the integrity of basal keratinocytes cytoskeleton. The majority of these defects are missense mutations in the rod domain, whose locations influence the disease severity. We investigated a large family dominantly affected with the Dowling-Meara form of EBS (EBS-DM). Sequencing of amplified and cloned K5 cDNA from cultured keratinocytes revealed a 66 nucleotide deletion in one allele corresponding to the last 22 amino acid residues encoded by exon 1 (Val164 to Lys185). Sequencing of amplified genomic DNA spanning the mutant region revealed a heterozygous G-to-A transition at + 1 position of the consensus GT donor splice site of intron 1 of K5. This mutation leads to the use of an exonic GT cryptic donor splice site, located 66 nucleotides upstream from the normal donor splice site of intron 1. The corresponding peptide deletion includes the last five amino acids of the H1 head domain and the first 17 amino acids of the conserved amino terminal end of the 1A rod domain, including the first two heptad repeats and the helix initiation peptide. The shortened polypeptide is expressed in cultured keratinocytes at levels which are comparable to the normal K5 protein. This is the first splice site mutation to be reported as a cause of EBS-DM. Owing to the functional importance of the removed region, our data strongly suggest that shortened keratin polypeptide can impair keratin filament assembly in a dominant manner and causes EBS-DM.

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Section: Consequences Of Abnormal Splicing Of Exonmentioning

confidence: 99%

Section: Proposed Mechanism Of Diseasementioning

confidence: 99%

Donor splice site mutation in keratin 5 causes in-frame removal of 22 amino acids of H1 and 1A rod domains in Dowling-Meara epidermolysis bullosa simplex

Rugg

Rochat

et al. 1999

Eur J Hum Genet

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“…On the basis of differences in molecular weight and pH, at least 20 different types of CKs have been identified. These are expressed in certain sets along various routes of epithelial differentiation in normal epithelium, tumor cells, and culture cells (Moll et al, 1982;Fuchs, 1988;Coulombe, 1993;Steinert, 1993). Cytokeratin 8 (CK8) and cytokeratin 19 (CK19) are specific cytoskeletal structures of simple epithelia, including bronchial epithelial cells (Moll et al, 1982;Fuchs, 1988;Coulombe, 1993;Steinert, 1993).…”

mentioning

confidence: 99%

Binding of Recombinant Human Cytokeratin 19 to Laminin. A Possible Role in Interaction between Intermediate Filament Derived from Epithelial Cells and Extracellular Matrixes.

Dobashi

Fujita

Murota

et al. 2000

Cell Struct. Funct.

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ABSTRACT. Cytokeratin 8 (CK8) and cytokeratin 19 (CK19) is a specific cytoskeletal component of simple epithelia, including bronchial epithelial cells. We hypothesized that CK8 or CK19 released from epithelial cells may bind to and cause damage to extracellular matrixes through binding of anti-CK8 or anti-CK19 autoantibodies. In the present study, bindings of recombinant human CK8 and CK19 to laminin (both derived from mouse sarcoma cells and human), collagen, gelatin, and fibronectin were evaluated by a modified enzyme-linked immunosorbent assay (ELISA). In addition, binding of CK19 to laminin was also confirmed by inhibition assay. As a result, CK19 strongly bound to mouse laminin as well as human laminin. Pretreatment with laminin significantly reduced the binding of CK19 to laminin. However, binding of recombinant CK19 to laminin was not demonstrated by Western immunoblot, suggesting that SDS treatment of laminin diminished the binding. These results suggest that released CK19 from epithelial cells may have played a role in the damage of basement membrane by accumulation of an immune complex composed by CK19 and anti-CK19 autoantibody.

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“…A critical aspect of keratinizing stratified epithelia is that the cells undergo a terminal differentiation program that results in the formation of a mechanically resistant surface composed of cornified cells filled with keratin filaments. This keratin envelope protects the underlying epithelial cells [19,20].…”

Section: Introductionmentioning

confidence: 99%

“…Keratin 19 is expressed in basal cells of non-keratinizing epithelia. K6 and K16 are constitutively expressed in different stratified epithelia, including the tongue, palate, gingiva, and esophagus [19,20]. Differentiating suprabasal cells of gingival tissue express keratins K1 and K10.…”

Section: Introductionmentioning

confidence: 99%

Engineered Keratinized Oral Mucosa Decreased C. albicans Transition Through the Production of Keratins 10, 14, 16, and 19 by Oral Epithelial Cells

Zakrzewski¹,

Rouabhia²

2007

TOMYCJ

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Abstract:The aim of this study was to evaluate the link between Candida albicans growth and dimorphism and the production of keratins by oral epithelial cells. Various culture models (monolayer and non-keratinized and keratinized engineered human oral mucosa) were produced and used for this purpose. Cell morphology, tissue structure, and the transition of C. albicans were assessed following cell and tissue infections. Keratin production by epithelial cells exposed to C. albicans was evaluated by Western blotting. Following contact with C. albicans, epithelial cells in the monolayer cultures showed differentiating phenotypes. Compared to the keratinized tissue, the non-keratinized mucosa displayed visible disorganization. The transition of C. albicans from blastospore to hyphal form was significantly lower in the keratinized oral mucosa model. This was correlated with the high levels of differentiating (K10) and proliferating (K14, K16, and K19) keratins in the keratinized tissue, suggesting that tissue stratification contributes to controlling C. albicans pathogenicity via keratin production. Thus, the transition of C. albicans from blastospore to hyphal form may be linked to keratin production. This may ultimately have implications in the control of oral candidiasis as well as in denture design to prevent denture stomatitis.

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Structure, Function, and Dynamics of Keratin Intermediate Filaments

Cited by 182 publications

References 55 publications

Donor splice site mutation in keratin 5 causes in-frame removal of 22 amino acids of H1 and 1A rod domains in Dowling-Meara epidermolysis bullosa simplex

Donor splice site mutation in keratin 5 causes in-frame removal of 22 amino acids of H1 and 1A rod domains in Dowling-Meara epidermolysis bullosa simplex

Binding of Recombinant Human Cytokeratin 19 to Laminin. A Possible Role in Interaction between Intermediate Filament Derived from Epithelial Cells and Extracellular Matrixes.

Engineered Keratinized Oral Mucosa Decreased C. albicans Transition Through the Production of Keratins 10, 14, 16, and 19 by Oral Epithelial Cells

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