Characterization of human loricrin. Structure and function of a new class of epidermal cell envelope proteins.

Hohl, Daniel; Mehrel, Thomas; Lichti, Ulrike; Turner, Maria L.; Roop, Dennis R.; Steinert, Peter M.

doi:10.1016/s0021-9258(18)38163-8

Cited by 282 publications

(45 citation statements)

References 61 publications

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“…Ninety-five percent of the whole HRNR consists in quasi-repetitive, glycine/serine-rich peptide sequences, which contain a number of aromatic (Tyr (Y), Phe (F), Trp (W)), and a few long-chain aliphatic (Val (V), Leu (L), Ile (I)) AAs (Figure 1). Domains with these structural motifs, termed ''glycine loops'' (Steinert et al, 1991), are found in keratins (Steinert et al, 1983), loricrin (Hohl et al, 1991) as well as corneodesmosin (Jonca et al, 2002). ''Glycine-loops'' have been associated with protein elastic behavior and protein motion as seen in Bombyx mori silk sericin, a protein glue that ensures the cohesion of the cocoon threads and spider silk proteins (Xu and Lewis, 1990;Smith et al, 1999;Altman et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Highly Complex Peptide Aggregates of the S100 Fused-Type Protein Hornerin Are Present in Human Skin

Meyer‐Hoffert

Reithmayer

et al. 2009

Journal of Investigative Dermatology

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Human hornerin (HRNR) is a 245 kDa S100 fused-type protein which contains 95% tandem quasi-repeating glycine- and serine-rich domains. Previously HRNR was not thought to be expressed in healthy skin; however, we purified an HRNR peptide fragment from stratum corneum. Moreover, we found that HRNR mRNA is expressed in skin biopsies from different sites as head, trunk, legs, hands, and feet. In cultured human epidermal keratinocytes, HRNR mRNA expression was transiently induced during Ca(2+)-dependent differentiation. Immunostaining using distinct antibodies generated against four putative HRNR domains revealed strong HRNR immunoreactivity in healthy epidermis as well as in the entire outer root sheath of normal human scalp hair follicles. In lesions from psoriasis and atopic dermatitis patients, HRNR immunoreactivity was reduced compared with uninvolved skin of these patients. Electrospray ionization mass spectrometry and Western blot analyses revealed that HRNR is a highly degradable protein that forms complex high molecular weight peptide aggregates. Our findings suggest that HRNR is expressed in healthy skin and give insight into the complex biology of this protein. HRNR and its degradation products might contribute to the barrier function of healthy human skin.

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Section: Discussionmentioning

confidence: 99%

Highly Complex Peptide Aggregates of the S100 Fused-Type Protein Hornerin Are Present in Human Skin

Meyer‐Hoffert

Reithmayer

et al. 2009

Journal of Investigative Dermatology

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“…The insolubility of corneocytes is primarily attributable to the ε-(γ-glutamyl) lysine cross-linkage formed between LOR and other prospective cross-linkage partners, keratins K1/K10 or FLG [35,36]. Thus, LOR organizes the higher-order structure of corneocytes [37]. Upon exposure to ambient air, LOR stabilizes corneocytes via extensive disulfide (-S-S-) cross-linkage formation, and possibly auto-oxidation [27,37], thus completing epidermal differentiation.…”

Section: Keratinization At a Glancementioning

confidence: 99%

“…Thus, LOR organizes the higher-order structure of corneocytes [37]. Upon exposure to ambient air, LOR stabilizes corneocytes via extensive disulfide (-S-S-) cross-linkage formation, and possibly auto-oxidation [27,37], thus completing epidermal differentiation.…”

Section: Keratinization At a Glancementioning

confidence: 99%

“…Thus, LOR organizes the higherorder structure of corneocytes [37]. Upon exposure to ambient air, LOR stabilizes corneocytes via extensive disulfide (-S-S-) cross-linkage formation, and possibly auto-oxidation [27,37], thus completing epidermal differentiation. Upon exposure to the ambient air, the keratinocyte cytoskeleton undergoes extensive disulfide formation in the SG and stabilizes corneocytes.…”

Section: Keratinization At a Glancementioning

confidence: 99%

“…In contrast to the conserved terminal domain features, internal domains constitute the modern fragments and thus reflect adaptive gene evolution [62][63][64]. For instance, the bulk sequence of Lor harbors many tandem peptide quasi-repeats of aliphatic (glycine/serine/cysteine) n , which differ markedly in size and sequence between the mouse and human homologs (Figure 3a) [37]. Similar genetic divergences are noted in Ivl, which shows substantial variance even among the hominoids, such as the human and the gorilla [61].…”

Section: The Evolution Of the Edc Gene Cluster; Analogy To The β-Globin Gene Clustermentioning

confidence: 99%

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The KEAP1/NRF2 Signaling Pathway in Keratinization

2020

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Keratinization is a tissue adaptation, but aberrant keratinization is associated with skin disorders such as ichthyoses, atopic dermatitis, psoriasis, and acne. The disease phenotype stems from the interaction between genes and the environment; therefore, an understanding of the adaptation machinery may lead to a new appreciation of pathomechanisms. The KEAP1/NRF2 signaling pathway mediates the environmental responses of squamous epithelial tissue. The unpredicted outcome of the Keap1-null mutation in mice allowed us to revisit the basic principle of the biological process of keratinization: sulfur metabolism establishes unparalleled cytoprotection in the body wall of terrestrial mammals. We summarize the recent understanding of the KEAP1/NRF2 signaling pathway, which is a thiol-based sensor-effector apparatus, with particular focuses on epidermal differentiation in the context of the gene-environment interaction, the structure/function principles involved in KEAP1/NRF2 signaling, lessons from mouse models, and their pathological implications. This synthesis may provide insights into keratinization, which provides physical insulation and constitutes an essential innate integumentary defense system.

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Development of a skin model based on insoluble fibrillar collagen

Geesin

Brown

Liu³

et al. 1996

J. Biomed. Mater. Res.

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A biocompatible, 3-dimensional, noncontracting, crosslinked collagen matrix was adapted to promote differentiation of epidermal keratinocytes. To produce the matrix, a 3% wt/wt dispersion of insoluble bovine collagen containing 5 mg polylysine/g collagen in 0.001 N HCl was blended, lyophilized, and crosslinked using a dehydrothermal technique. Matrices 4 cm2 and 3 mm thick were seeded with human dermal fibroblasts (1 x 10(5)/cm2). After 5 days in culture, the matrices were seeded with human epidermal keratinocytes (1 x 10(5)/cm2). The cultures were grown submerged for 1 week and raised to the liquid/air interface for 3 weeks to promote epidermal differentiation. Based on morphology and immunological staining with antibodies for human involucrin, keratin 1 (k1), filaggrin, and loricrin, the state of differentiation of the epidermal layer was nearly equivalent to that seen with cultures grown on contracted collagen lattices produced according to the methodology described in the literature and similar to the pattern produced in normal neonatal foreskin. These results demonstrate the usefulness of an in vitro skin model employing a crosslinked collagen matrix that permits the incorporation of additional covalently linked bioactive molecules during matrix formation.

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Characterization of human loricrin. Structure and function of a new class of epidermal cell envelope proteins.

Cited by 282 publications

References 61 publications

Highly Complex Peptide Aggregates of the S100 Fused-Type Protein Hornerin Are Present in Human Skin

Highly Complex Peptide Aggregates of the S100 Fused-Type Protein Hornerin Are Present in Human Skin

The KEAP1/NRF2 Signaling Pathway in Keratinization

Development of a skin model based on insoluble fibrillar collagen

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