DOCSLIB.ORG

Structures of the ß-Keratin Filaments and Keratin Intermediate Filaments in the Epidermal Appendages of Birds and Reptiles (Sauropsids)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Structures of the ß-Keratin Filaments and Keratin Intermediate Filaments in the Epidermal Appendages of Birds and Reptiles (Sauropsids) G C A T T A C G G C A T genes Review Structures of the ß-Keratin Filaments and Keratin Intermediate Filaments in the Epidermal Appendages of Birds and Reptiles (Sauropsids) David A.D. Parry School of Fundamental Sciences, Massey University, Private Bag 11-222, Palmerston North 4442, New Zealand; [email protected]; Tel.: +64-6-9517620; Fax: +64-6-3557953 Abstract: The epidermal appendages of birds and reptiles (the sauropsids) include claws, scales, and feathers. Each has specialized physical properties that facilitate movement, thermal insulation, defence mechanisms, and/or the catching of prey. The mechanical attributes of each of these appendages originate from its fibril-matrix texture, where the two filamentous structures present, i.e., the corneous ß-proteins (CBP or ß-keratins) that form 3.4 nm diameter filaments and the α-fibrous molecules that form the 7–10 nm diameter keratin intermediate filaments (KIF), provide much of the required tensile properties. The matrix, which is composed of the terminal domains of the KIF molecules and the proteins of the epidermal differentiation complex (EDC) (and which include the terminal domains of the CBP), provides the appendages, with their ability to resist compression and torsion. Only by knowing the detailed structures of the individual components and the manner in which they interact with one another will a full understanding be gained of the physical properties of the tissues as a whole. Towards that end, newly-derived aspects of the detailed conformations of the two filamentous structures will be discussed and then placed in the context of former knowledge. Citation: Parry, D.A.D. Structures of the ß-Keratin Filaments and Keratin Keywords: corneous ß-proteins; keratin intermediate filaments; X-ray fiber diffraction Intermediate Filaments in the Epidermal Appendages of Birds and Reptiles (Sauropsids). Genes 2021, 12, 591. https://doi.org/10.3390/ 1. Introduction genes12040591 Structural studies on the epidermal appendages of birds and reptiles (sauropsids) pre- sented in this review will draw on data, not only from the birds, but also from the crocodiles, Academic Editor: Matthew Greenwold turtles, lizards, snakes, and tuatara. An appreciation of the relationships between these vertebrates is, therefore, of some value and towards that end the phylogenetic classification Received: 18 February 2021 of the sauropsids is shown in Figure1. This illustrates that the archelosaurs diverged into Accepted: 15 April 2021 the archosaurs (birds and crocodiles) and the testudines (turtles) about 272 Mya, and that Published: 17 April 2021 the lepidosaurs diverged in to the squamates (lizards and snakes) and the rhynchocephalia (tuatara) about 230 Mya [1–4]. Whilst this diversification will necessarily result in impor- Publisher’s Note: MDPI stays neutral tant differences between the species it is expected that major similarities will remain, a with regard to jurisdictional claims in supposition borne out by much of the data presented here. published maps and institutional affil- iations. Electron microscopy investigations of the cross-sections of the hard keratins constitut- ing the epidermal appendages (feathers, claws, scales) of the sauropsids have shown that these tissues have a filament-matrix texture [6–12]. This is dominated by filaments about 3.4 nm in diameter that provide much of the tensile strength of the tissue (Figure2). The matrix formed by the terminal domains of the filament-forming corneous ß-proteins (CBP) Copyright: © 2021 by the author. and the other proteins of the epidermal differentiation complex (EDC) [13], in contrast, has Licensee MDPI, Basel, Switzerland. an important role in specifying hardness, toughness, pliability, compression attributes, and This article is an open access article resistance to torsion and flexibility [14–22]. A second type of filament, about 7–10 nm in distributed under the terms and conditions of the Creative Commons diameter, has also been observed in these appendages. These filaments—the keratin inter- Attribution (CC BY) license (https:// mediate filaments (KIF)—are less common than their smaller counterparts [23] and tend creativecommons.org/licenses/by/ to occur in discrete layers akin to those sometimes seen in the mammalian hard keratins, 4.0/). Genes 2021, 12, 591. https://doi.org/10.3390/genes12040591 https://www.mdpi.com/journal/genes Genes 2021, 12, x FOR PEER REVIEW 2 of 21 Genes 2021, 12, 591 2 of 19 Genes 2021, 12, x FOR PEER REVIEW 2 of 21 such as hair and quill [24–30]. Their terminal domains, likewise, form an important part of the matrix structure. Figure 1. Phylogenetic classification of the sauropsids. The branching times are measured in millions of years (Mya) and are based on studies of mitochondrial DNA [1]. Figure reproduced from [5] with permission of Elsevier. Electron microscopy investigations of the cross-sections of the hard keratins consti- tuting the epidermal appendages (feathers, claws, scales) of the sauropsids have shown that these tissues have a filament-matrix texture [6–12]. This is dominated by filaments about 3.4 nm in diameter that provide much of the tensile strength of the tissue (Figure 2). The matrix formed by the terminal domains of the filament-forming corneous ß-proteins (CBP) and the other proteins of the epidermal differentiation complex (EDC) [13], in con- trast, has an important role in specifying hardness, toughness, pliability, compression at- tributes, and resistance to torsion and flexibility [14–22]. A second type of filament, about 7–10 nm in diameter, has also been observed in these appendages. These filaments—the keratin intermediate filaments (KIF)—are less common than their smaller counterparts [23] and tend to occur in discrete layers akin to those sometimes seen in the mammalian Figure 1. Phylogenetic classificationclassificationhard keratins, of the sauropsids.sasuchuropsids. as hair The and branching quill [24–30]. times Their are measuredmeasurterminaled domains, in millions likewise, of years form (Mya) an and are based on studies ofof mitochondrialmitochondrialimportant DNADNA part of [[1].1 ].the Figure matrix reproducedreproduced structure. fromfrom [[5]5] withwith permissionpermission ofof Elsevier.Elsevier. Electron microscopy investigations of the cross-sections of the hard keratins consti- tuting the epidermal appendages (feathers, claws, scales) of the sauropsids have shown that these tissues have a filament-matrix texture [6–12]. This is dominated by filaments about 3.4 nm in diameter that provide much of the tensile strength of the tissue (Figure 2). The matrix formed by the terminal domains of the filament-forming corneous ß-proteins (CBP) and the other proteins of the epidermal differentiation complex (EDC) [13], in con- trast, has an important role in specifying hardness, toughness, pliability, compression at- tributes, and resistance to torsion and flexibility [14–22]. A second type of filament, about 7–10 nm in diameter, has also been observed in these appendages. These filaments—the keratin intermediate filaments (KIF)—are less common than their smaller counterparts [23] and tend to occur in discrete layers akin to those sometimes seen in the mammalian hard keratins, such as hair and quill [24–30]. Their terminal domains, likewise, form an important part of the matrix structure. Figure 2. Transmission electron micrograph of a cross-section of feather keratin showing filaments about 3–4 nm in diameter [6]. Figure reproduced from [31] with permission of Elsevier. Over the past 20 years, hundreds of sequences of closely related families of corneous ß-proteins (CBP, also known as ß-keratins; [32,33]) have been published. These sequences represent every branch in the phylogenetic classification of the birds and reptiles and include, for example, those from chicken and zebra finch [34], crocodile and alligator [28,35], turtle [29], tuatara [33,36], green anole lizard [37], and snake [26]. Chains from each of these protein families form the 3.4 nm diameter filaments that exist in that particular species. A much smaller number of sequences of the closely related families of chains that assemble to form the 7–10 nm KIF in the sauropsids have been published thus far (Anolis carolinensis,[38–40]; Sphenodon punctatus,[36]). Both sets of sequence data (CBP and KIF) have provided new insights into the structures of the two filament types, and these will be described in Sections2 and3, respectively. Genes 2021, 12, 591 3 of 19 X-ray diffraction studies on the 3.4 nm filaments and their constituent CBPs have largely been confined to those based on seagull feather rachis (Larus novae-hollandiae). This material in its natural form contains highly orientated filament bundles, thereby making the rachis ideally suited to provide the most detailed X-ray patterns possible (Figure3a). The well-defined row lines present that indicate lateral order (Figure3c) can be removed by pressing the specimen in steam (Figure3d). Less detailed X-ray data have also been obtained from other materials, including goanna claw (Figure3e; Varanus varius,[24]), chicken scale (Gallus gallus domesticus,[41]), snake scale (unidentified species,[24]) and tuatara Genes 2021, 12, x FOR PEER REVIEW 4 of 21 claw [42]. Figure 3. High angle X-ray diffractions patterns of (a) seagull feather rachis (Larus novae-hollandiae), which shows features of a Figure 3. High angle X-ray diffractions patterns of (a) seagull feather rachis (Larus novae-hollandiae), which shows features ß-conformation,of a ß-conformation, and (b) porcupine and (b) quill porcupine (Hystrix quill cristata(Hystrix), cristata which), which is based is based on theon theα-conformation α-conformation with with its its characteristic characteristic 0.51 nm meridional reflection0.51 nm meridional and the reflection 0.98 nm and equatorial the 0.98 nm and equatorial near-equatorial and near-equatorial reflections, reflections, (c,d) show (c,d) show the samethe same seagull seagull feather rachis feather rachis before and after pressing in steam to remove the lateral organisation between the filaments and (e) goanna before and afterclaw ( pressingVaranus varius in steam).
Load more

Recommended publications
  • A Significant Soluble Keratin Fraction In
    Journal of Cell Science 105, 433-444 (1993) 433 Printed in Great Britain © The Company of Biologists Limited 1993 A significant soluble keratin fraction in ‘simple’ epithelial cells Lack of an apparent phosphorylation and glycosylation role in keratin solubility Chih-Fong Chou*, Carrie L. Riopel, Lusijah S. Rott and M. Bishr Omary† Palo Alto Veterans Administration Medical Center and the Digestive Disease Center at Stanford University, School of Medicine, 3801 Miranda Avenue, GI 111, Palo Alto, CA 94304, USA *Author for reprint requests †Author for correspondence SUMMARY We studied the solubility of keratin polypeptides 8 and aments in vitro as determined by electron microscopy. 18 (K8/18), which are the predominant intermediate fil- Cross-linking of soluble K8/18 followed by immunopre- aments in the human colonic epithelial cell line HT29. cipitation resulted in dimeric and tetrameric forms, We find that asynchronously growing cells (G0/G1 stage based on migration in SDS-polyacrylamide gels. In of the cell cycle) have a substantial pool of soluble ker- addition, cross-linked and native soluble K8/18 showed atin that constitutes approx. 5% of total cellular ker- similar migration on nondenaturing gels and similar atin. This soluble keratin pool was observed after sedimentation after sucrose density gradient centrifu- immunoprecipitation of K8/18 from the cytosolic frac- gation. Our results indicate that simple epithelial ker- tion of cells disrupted using three detergent-free meth- atins are appreciably more soluble than previously rec- ods. Several other cell lines showed a similar significant ognized. The soluble keratin form is assembly competent soluble cytosolic K8/18 pool.
    [Show full text]
  • Since 1992 There Have Been Many Products Marketed As Cosmetics Designed to Exfoliate the Skin 1 2
    SCCNFP/0370/00, final The Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP) has been requested to give an opinion on the safety of alpha-Hydroxy Acids in cosmetic products. The attached Position Paper of the SCCNFP has been prepared in this respect. The Commission services invite interested parties for their comments. Please send your comments before 15 September 2000 at the following e-mail address : [email protected] SCCNFP/0370/00, final The safety of alpha-Hydroxy acids ____________________________________________________________________________________________ THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS. POSITION PAPER CONCERNING THE SAFETY OF ALPHA-HYDROXY ACIDS Adopted by the SCCNFP during the 13th plenary meeting of 28 June 2000 2 SCCNFP/0370/00, final The safety of alpha-Hydroxy acids ____________________________________________________________________________________________ 1. Terms of reference The safety of α-hydroxy acids in cosmetic products has been questioned by some Member States with respect to their dermal tolerance. Hydroxy acids have a long history of use in dermatological preparations and recently have become important ingredients in cosmetics. Concerns on both the dermal and systemic safety of these materials has led to calls for their listing in Annex III (List of substances which cosmetic products must not contain except subject to restrictions and conditions laid down) to the Cosmetics Directive 76/768/EEC. 2. Position of the SCCNFP Definition of AHAs AHAs are carboxylic acids substituted with a hydroxyl group on the alpha carbon. The AHAs most commonly used in cosmetic products are glycolic acid and lactic acid.
    [Show full text]
  • Corneocytes Undergo Systematic Changes in Element Concentrations Across the Human Inner Stratum Corneum
    Corneocytes Undergo Systematic Changes in Element Concentrations Across the Human Inner Stratum Corneum Ronald R. Warner, Rodney D. Bush, and Nick A. Ruebusch Miami Valley Laboratories, Procter & Gamble Co., P.O. Box 538707, Cincinnati, Ohio, U .S.A. Using analytical electron microscopy of freeze-dried (as potassium declines), and then decreases to values cryosections, physiologic elements were visualized comparable to those in the innermost corneocyte. within individual cells across the human inner stra­ The cellular sodium concentration (per unit volume tum corneum. Human corneocytes undergo system­ of tissue) is relatively unaltered in transit across the atic changes in element composition as they advance inner stratum corneum. The initial potassium and through this region. Phosphorus is largely excluded chloride movements are oppositely directed and have from the stratum corneum, undergoing a precipitous the appearance of creating an electrical charge drop in concentration at the granular/stratum cor­ imbalance. The position-dependent alterations in neum interface. The cellular potassium concentra­ corneocyte elemental composition may reflect se­ tion has a profile similar to that of phosphorus but quential stages of chemical maturation occurring with a slower decline, thus migrating further into the intracellularly during stratum corneum transit, an stratum corneum. In contrast, the cellular chloride example of which is the breakdown of filaggrin that concentration increases in the innermost corneocyte occurs over this same region of the inner stratum layer, increases further in the subsequent layer or two corneum. ] Invest Dermatol 104:530-536, 1995 he stratuin corneum (SC) has often been considered Hkely reflect innate biochemical alterations occurring intracellularl y homogeneous in its structure and its barrier proper­ as cells transform from a viable granular layer into "mature" ties [1,2], but this concept is increasingly difficult to corneocytes within the unique SC environment.
    [Show full text]
  • The Epidermal Lamellar Body: a Fascinating Secretory Organelle
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE See relatedprovided article by Elsevier on page- Publisher 1137 Connector The Epidermal Lamellar Body: A Fascinating Secretory Organelle Manige´ Fartasch Department of Dermatology, University of Erlangen, Germany The topic of the function and formation of the epidermal LAMP-1. Instead, it expresses caveolin—a cholesterol- permeability barrier continue to be an important issue to binding scaffold protein that facilitates the assembly of understand regulation and development of the normal and cholesterol—and sphingolipids into localized membrane abnormal epidermis. A major player in the formation of the domains or ‘‘rafts’’ (Sando et al, 2003), which typically serve barrier, i.e., the stratum corneum (SC), is a tubular and/or as targets for apical transport of vesicles of Golgi origin. To ovoid-shaped membrane-bound organelle that is unique to date, a large body of evidence supports the concept that mammalian epidermis. In the past, this organelle has been LB, which shows morphology ranging from vesicles to embellished largely with descriptive names attributed to tubules on EM, are probably products of the tubulo- its perceived functional properties like membrane coating vesicular elements of the trans-Golgi network (TGN) that granule, keratinosome, cementsoms, and lamellar body/ is a tubulated sorting and delivery portion of the Golgi granule (LB). Over the last decade, data from several apparatus (Elias et al, 1998; Madison, 2003). Recently, laboratories documented
    [Show full text]
  • Antiaging Effects of Topical Lactobionic Acid: Results of a Controlled Usage Study Barbara A
    STUDY Antiaging Effects of Topical Lactobionic Acid: Results of a Controlled Usage Study Barbara A. Green, RPh, MS; Brenda L. Edison, BA; Monya L. Sigler, PhD There are numerous clinical publications supporting the use of traditional a-hydroxy acids (AHAs), including glycolic acid, lactic acid, and citric acid, to counter aging. Studies have demonstrated sig- nificant dermal effects, including increased deposition of glycosaminoglycans, improved elastic fiber quality, and collagen gene induction. These dermal effects provide antiaging benefits to skin. Lacto- bionic acid, a next-generation AHA possessing a polyhydroxy structure (a so-called polyhydroxy acid), has been shown to provide textural and smoothing benefits to skin and to increase skin thickness via digital caliper measurements, thereby providing multiple antiaging benefits. Lactobionic acid is also an antioxidant chelating substance that suppresses matrix metalloproteinase enzymatic activity, helping to protect against further sunCOS damage. Lactobionic acidDERM has also been shown to be gentle to skin without causing the stinging and irritation associated with some AHAs. This study was conducted to assess the efficacy of topical lactobionic acid 8% to reduce the visible signs of aging skin on the face and to deter- mine histologic and dermalDo thickness Not changes on the armCopy during 12 weeks of controlled usage. Results indicate significant improvements in clinically graded parameters, a significant reduction in mild pre- existing irritation, and significant increases in skin firmness and thickness. Histologic examples of reduced matrix metalloproteinase-9 activity and increased staining for glycosaminoglycans were observed. When used alone, either as a preventive or an active treatment, lactobionic acid provides beneficial antiaging effects.
    [Show full text]
  • A Dysfunctional Desmin Mutation in a Patient with Severe Generalized Myopathy
    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 11312–11317, September 1998 Genetics A dysfunctional desmin mutation in a patient with severe generalized myopathy ANA M. MUN˜OZ-MA´RMOL*†‡,GERALDINE STRASSER‡§,MARCOS ISAMAT*†,PIERRE A. COULOMBE¶,YANMIN YANG§, i XAVIER ROCA†,ELENA VELA*†,JOSE´ L. MATE†,JAUME COLL ,MARI´A TERESA FERNA´NDEZ-FIGUERAS†, JOSE´ J. NAVAS-PALACIOS†,AURELIO ARIZA†, AND ELAINE FUCHS§** *Fundacio´n Echevarne, 08037 Barcelona, Spain; Departments of †Pathology and iNeurology, Hospital Universitari Germans Trias i Pujol, Universitat Auto´noma de Barcelona, 08916 Badalona, Barcelona, Spain; ¶Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205; and §Howard Hughes Medical Institute and Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637 Contributed by Elaine Fuchs, July 29, 1998 ABSTRACT Mice lacking desmin produce muscle fibers desmin functions in cellular transmission of both active and with Z disks and normal sarcomeric organization. However, passive force (14, 15). the muscles are mechanically fragile and degenerate upon Desminopathies are a heterogeneous group of human myop- repeated contractions. We report here a human patient with athies characterized by abnormal aggregations of desmin in severe generalized myopathy and aberrant intrasarcoplasmic skeletal andyor cardiac muscle fibers (for review, see ref. 16). The accumulation of desmin intermediate filaments. Muscle tissue clumping of desmin in muscle cells of these patients bears a from this patient lacks the wild-type desmin allele and has a striking resemblance to the keratin aggregates that accumulate in desmin gene mutation encoding a 7-aa deletion within the degenerating epithelial cells of various human keratin disorders coiled-coil segment of the protein.
    [Show full text]
  • Stratum Corneum Moisturization at the Molecular Level
    Abridged from the Dermatology Progress in Foundation Dermatology Editor: Alan N. Moshell , MD. Stratum Corneum Moisturization at the Molecular Level Anthony V. Rawlings, Ian R. Scott, Clive R. Harding, * and Paul A. Bowsed Unilever Research, Edgewater Laboratory, Edgewater, N ew Jersey, U .S.A.; ' Unilevcr Research, Colworth Laboratory, Sharnbrook, Bedford; and tUnilever Research, Port Sunlight Laboratory, Bebington, Wirral, U.K. n any living system, control of water translocation is essential corneocytes embedded in a lipid matrix (see Fig 1). The main func­ for survival. Being in close proximity to a non-aqueous envi­ tion of the epidermis is to produce the stratum corneum; a selec­ ronment this control is a fundamental property of our skin tively permeable outer layer that protects against water loss and and it uses mechanisms that are complex, elegant, and unique chemical insult. However, as will become evident from this review, in nature to achieve it. the barrier function of the stratum corneum is not its only function. IThe skin preserves water through intercellular occlusion (water The combination of the barrier properties of the stratum corneum permeability barrier) and cellular humectancy (natural moisturizing and its inherent cellular humectant capabilities moisturize the stra­ factor or NMF). The mechanisms for producing the water perme­ tum corneum, which is important for maintaining the flexibility of ability barrier and NMF are not only complex but also susceptible to the stratum corneum and its desquamation. The most characterized disturbance and perturbation. components of the stratum corneum are keratins, specialized cor­ This review begins with an overview of the vast amount of work neocyte envelope proteins, lipids, NMF, specialized adhesion struc­ that has led to a greater understanding of the mechanisms of mois­ tures (desmosomes), and enzymes.
    [Show full text]
  • Keratins Determine Network Stress Responsiveness in Reconstituted Actin-Keratin Filament Systems
    bioRxiv preprint doi: https://doi.org/10.1101/2020.12.27.424392; this version posted December 28, 2020. The copyright holder for this preprint (which was not certified by peer review)Please is the author/funder, do not adjust who margins has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. ARTICLE Keratins determine network stress responsiveness in reconstituted actin‐keratin filament systems† *af‡ ab‡ ab cd *abe Iman Elbalasy , Paul Mollenkopf , Cary Tutmarc , Harald Herrmann and Jörg Schnauß The cytoskeleton is a major determinant of cell mechanics, a property that is altered during many pathological situations. To understand these alterations, it is essential to investigate the interplay between the main filament systems of the cytoskeleton in the form of composite networks. Here, we investigate the role of keratin intermediate filaments (IFs) in network strength by studying in vitro reconstituted actin and keratin 8/18 composite networks via bulk shear rheology. We co‐polymerized these structural proteins in varying ratios and recorded how their relative content affects the overall mechanical response of the various composites. For relatively small deformations, we found that all composites exhibited an intermediate linear viscoelastic behavior compared to that of the pure networks. In stark contrast, the composites displayed increasing strain stiffening behavior as a result of increased keratin content when larger deformations were imposed. This strain stiffening behavior is fundamentally different from behavior encountered with vimentin IF as a composite network partner for actin. Our results provide new insights into the mechanical interplay between actin and keratin in which keratin provides reinforcement to actin.
    [Show full text]
  • 2 Current Knowledge Status of the Stratum Corneum Structure and Transdermal Permeation Enhancement
    2. CURRENT KNOWLEDGE STATUS 2 Current knowledge status of the stratum corneum structure and transdermal permeation enhancement 2.1 The organization of the mammalian skin The skin consists of three distinct layers [2, 8]. The subcutis and the dermis , forming the bulk of skin, are made up of adipose and connective tissue elements, respectively. The overlying, avascular epidermis is composed primarily of keratinocytes and is divisible into four layers, namely the stratum basale, spinosum, granulosum, and corneum [2]. These layers present different stages of the cell differentiation, termed keratinisation . The continuously dividing stem cells on the basal layer generate columns of keratinocytes, which finally differentiate into the flattened corneocytes (Fig. 2.1). The innermost epidermal layer, the stratum basale, is a single layer of columnar basal cells that remain attached to the basement membrane via hemidesmosomes. The next epidermal layer, the stratum spinosum , has a spiny appearance of its cells in histological sections due to the abundance of desmosomes. First in this layer, lamellar bodies (also called membrane coating granules, keratinosomes or Odland bodies) and increased amount of keratin filaments can be detected. In the stratum granulosum , a quantitative increase in keratin synthesis occurs. The keratohyalin granules containing proteins (profillaggrin, loricrin and keratin) become progressively larger and give the name to this layer. Simultaneously, the uppermost cells in the stratum granulosum display a unique structural and functional organization of the lamellar bodies consistent with their readiness to terminally differentiate into a corneocyte, during which the lamellar bodies are secreted to the intercellular domains. The uppermost layer of the epidermis, the SC, creates the main skin barrier.
    [Show full text]
  • Biological Functions of Cytokeratin 18 in Cancer
    Published OnlineFirst March 27, 2012; DOI: 10.1158/1541-7786.MCR-11-0222 Molecular Cancer Review Research Biological Functions of Cytokeratin 18 in Cancer Yu-Rong Weng1,2, Yun Cui1,2, and Jing-Yuan Fang1,2,3 Abstract The structural proteins cytokeratin 18 (CK18) and its coexpressed complementary partner CK8 are expressed in a variety of adult epithelial organs and may play a role in carcinogenesis. In this study, we focused on the biological functions of CK18, which is thought to modulate intracellular signaling and operates in conjunction with various related proteins. CK18 may affect carcinogenesis through several signaling pathways, including the phosphoinosi- tide 3-kinase (PI3K)/Akt, Wnt, and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling pathways. CK18 acts as an identical target of Akt in the PI3K/Akt pathway and of ERK1/2 in the ERK MAPK pathway, and regulation of CK18 by Wnt is involved in Akt activation. Finally, we discuss the importance of gaining a more complete understanding of the expression of CK18 during carcinogenesis, and suggest potential clinical applications of that understanding. Mol Cancer Res; 10(4); 1–9. Ó2012 AACR. Introduction epithelial organs, such as the liver, lung, kidney, pancreas, The intermediate filaments consist of a large number of gastrointestinal tract, and mammary gland, and are also nuclear and cytoplasmic proteins that are expressed in a expressed by cancers that arise from these tissues (7). In the tissue- and differentiation-dependent manner. The compo- absence of CK8, the CK18 protein is degraded and keratin fi intermediate filaments are not formed (8).
    [Show full text]
  • Inability of Keratinocytes Lacking Their Specific Transglutaminase To
    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 687–690, January 1998 Medical Sciences Inability of keratinocytes lacking their specific transglutaminase to form cross-linked envelopes: Absence of envelopes as a simple diagnostic test for lamellar ichthyosis SAEWHA JEON*, PHILIPPE DJIAN†, AND HOWARD GREEN*‡ *Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115; and †Centre National de la Recherche Scientifique, Centre de Recherche sur l’Endocrinologie Mole´culaireet le De´veloppement,9 rue Jules Hetzel, 92190 Meudon, France Contributed by Howard Green, November 14, 1997 ABSTRACT Epidermal keratinocytes, late in their termi- cross-linked envelopes are formed. The diagnosis of TGase- nal differentiation, form cross-linked envelopes resistant to negative lamellar ichthyosis can be readily made by simple ionic detergent and reducing agent. Because the cross-linking inspection under the microscope. process is catalyzed by the keratinocyte transglutaminase, the absence of active transglutaminase should result in failure of MATERIALS AND METHODS the keratinocyte to form a cross-linked envelope. Three ke- ratinocyte strains bearing mutations in the keratinocyte Cell Culture. Human epidermal keratinocytes were culti- transglutaminase were examined: two contained no detectable vated on lethally irradiated 3T3-J2 feeders in FAD medium transglutaminase mRNA and none contained active enzyme. containing supplements (31). For all the experiments, cells at All three were unable to form cross-linked envelopes, either lower than passage 5 were grown to confluence and harvested. spontaneously in stratified cultures or upon induction with Northern and Western Blots. Total RNA was isolated by Ca21. Although stratum corneum of normal humans and using Rneasy total RNA kit (Qiagen, Chatsworth, CA).
    [Show full text]
  • Epidermal Corneocytes: Dead Guards of the Hidden Treasure
    EPIDERMAL CORNEOCYTES: DEAD GUARDS OF THE HIDDEN TREASURE AV Mezentsev Center for Radiological Research, Columbia University NY, New York, USA Key words: epidermis, keratinization, corneocytes, proliferation, differentiation, stem cells, cell signaling, proteolysis. Acknowledgements: Abbreviations: 7-DHC, 7-dehydrocholesterol; VDR, vitamin D receptor; PLC, phospholipase C, PIP2, phosphatidylinositols; IP3, inositol triphosphate; DAG, diacylglycerol; TGM, transglutaminase(s); ALP, antileukoproteinase; LEKTI, lymphoepithelial Kazal-type 5 serine protease inhibitor; SCCE, corneum chymotryptic enzyme; SCTE, stratum corneum tryptic enzyme; MT-SP1, Matriptase. Abstract Gradual transformation of the epidermal stem cells to corneocytes involves a chain of chronologically well-arranged events that mostly stimulated locally by their neighbors. Cell diversity that observed during the differentiation through the different epidermal cell layers included the consisted changes of cell shape, intercellular contacts and proliferation. However, the most dramatically these changes appeared at the molecular level through gene expression, catalysis and intraprotein interactions. The proposed review explains these changes by switching systemic transcription factors that unlike their counterparts those role is limited to a contribution to gene expression also prepare cells to the next step of differentiation via modification of the chromatin pattern . Since primary epidermal keratinocytes are one of the most easy available type of the stem cells, a better understanding of the epidermal differentiation will benefit the research in the other areas by a discovery of basic coordinating mechanisms that stand behind such distinct molecular events as cell signaling and gene expression, and formulate basic principles for a smart therapeutic correction of the metabolism. Introduction As the most outer tissue of the body, the epidermis protects it from physical and chemical insults and infections.
    [Show full text]