DOCSLIB.ORG

Ishikawa 2010.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Ishikawa 2010.Pdf Journal of Dermatological Science 60 (2010) 95–104 Contents lists available at ScienceDirect Journal of Dermatological Science journal homepage: www.elsevier.com/jds Epiplakin accelerates the lateral organization of keratin filaments during wound healing Kazushi Ishikawa a,b, Hideaki Sumiyoshi b, Noritaka Matsuo b, Naoko Takeo a, Mizuki Goto a, Osamu Okamoto a, Shuji Tatsukawa c, Hirokazu Kitamura c, Yoshihisa Fujikura c, Hidekatsu Yoshioka b, Sakuhei Fujiwara a,* a Department of Dermatology, Faculty of Medicine, Oita University, Hasama-machi, Oita, Japan b Department of Matrix Biology, Faculty of Medicine, Oita University, Hasama-machi, Oita, Japan c Department of Molecular Anatomy, Faculty of Medicine, Oita University, Hasama-machi, Oita, Japan ARTICLE INFO ABSTRACT Article history: Background: Epiplakin (EPPK) belongs to the plakin family of cytolinker proteins and, resembling other Received 7 March 2010 members of the plakin family such as BPAG1 (an autoantigen of bullous pemphigoid) and plectin, EPPK Received in revised form 3 August 2010 has plakin repeat domains (PRDs) that bind to intermediate filaments. Elimination of EPPK by gene Accepted 25 August 2010 targeting in mice resulted in the acceleration of keratinocyte migration during wound healing. EPPK is expressed in proliferating keratinocytes at wound edges and, in view of its putative function in binding Keywords: to keratin, we postulated that the keratin network in EPPK-null (EPPKÀ/À) mice might be disrupted Bullous pemphigoid during wound healing. Epiplakin Objective: To examine this hypothesis and to determine the precise localization of EPPK in relation to Keratin À/À Keratinocyte keratin filaments, we compared the non-wounded and wounded epidermis of wild-type and EPPK mice. À/À Wound healing Methods: Non-wounded epidermis and wounded epidermis from wild-type and EPPK mice were examined by immunofluorescence staining and electron microscopy before and after double immunostaining. Results: EPPK was colocalized with keratin 17 (K17) more extensively than with other keratins examined in wounded epidermis. The expression of K5, K10, K6, and K17 was the same in EPPKÀ/À mice after wounding as in normal mice, but diameters of keratin filaments were reduced in EPPKÀ/À keratinocytes. Electron microscopy after immunostaining revealed that EPPK colocalized with K5, K10 and K6 after wounding in wild-type mice. Conclusion: Our data indicate that EPPK accelerates keratin bundling in proliferating keratinocytes during wound healing and suggest that EPPK might contribute to reinforcement of keratin networks under mechanical stress. ß 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved. 1. Introduction spacing comprised of so-called linker regions [1,2]. As in the case of other members of the plakin family, namely, BPAG1 (an autoanti- Epiplakin (EPPK) belongs to the plakin family of cytolinker gen of bullous pemphigoid) and plectin, experiments in vitro have proteins. It is expressed mainly in the upper layers of the epidermis demonstrated that the PRDs and/or linker regions of EPPK bind to and it was identified as an antigen in autoimmune blistering intermediate filaments [3–5]. disease [1]. EPPK is a plakin but has some unusual features. Human To examine the functions of EPPK, we generated EPPKÀ/À mice. EPPK has 13 domains and mouse EPPK has 16 domains that are Under normal conditions, there were no detectable differences homologous to the B domain, one of the plakin repeat domains between wild-type and EPPKÀ/À mice. However, wounds on the backs (PRDs) found in the carboxy-terminal region of desmoplakin. of EPPKÀ/À mice closed more rapidly than those on the backs of wild- These domains are distributed along the entire amino acid type mice and of heterozygous mice. At wound edges in wild-type sequences of human and murine EPPK with relatively uniform mice, EPPK was expressed in proliferating keratinocytes; in EPPKÀ/À mice, there seemed to be fewer proliferating keratinocytes [6]. We postulated that EPPK might be linked, functionally, to * Corresponding author. Tel.: +81 97 586 5882; fax: +81 97 586 5889. keratin networks during wound healing and, in the present study, E-mail address: [email protected] (S. Fujiwara). we examined the relationship between the expression and 0923-1811/$36.00 ß 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jdermsci.2010.08.011 96 K. Ishikawa et al. / Journal of Dermatological Science 60 (2010) 95–104 localization of EPPK on the other hand and the formation and incubated for 2 h at room temperature, in darkness with two of the characteristics of keratin networks during wound healing. following four reagents:(1) Alexa Fluor 488-conjugated antibodies raised in goat against mouse IgG (diluted 1:1000; Molecular Probes, 2. Materials and methods Eugene, OR, USA); (2) Alexa Fluor 488-conjugated antibodies raised in goat against rabbit IgG (diluted 1:1000; Molecular Probes); (3) 2.1. Expression of glutathione S-transferase-tagged (GST-tagged) Alexa Fluor 568-conjugated antibodies raised in goat against rat IgG fusion proteins and preparation of polyclonal antibodies (diluted 1:1000; Molecular Probes); and (4) Alexa Fluor 594- conjugated antibodies raised in goat against mouse IgG (diluted Glutathione S-transferase-EPPK (GST-EPPK) fusion protein, 1:1000; Molecular Probes). Immunofluorescence-labelled sections which included the linker region between the 15th and 16th B were rinsed in PBS and mounted on glass slides with Vectashield1 domains of mouse EPPK [6], and GST-keratin 5 (GST-K5) fusion anti-fade solution (Vector Laboratories, Burlingame, CA, USA) and protein, which included the carboxy-terminal region of mouse K5 coverslips. Sections were analyzed with a confocal laser scanning were expressed in E. coli. The purified recombinant proteins were microscope (LSM5 PASCAL, Carl Zeiss, Jena, Germany). For genera- mixed, separately, with an equal volume of Freund’s complete tion and analysis of composite images, we used Adobe Photoshop adjuvant (Difco, Detroit, MI, USA) and injected subcutaneously into (version 7.0; Adobe Systems, San Jose, CA, USA). rabbits (EPPK) or rats (EPPK and K5). The animals were given two subsequent booster injections plus Freund’s incomplete adjuvant 2.4. Electron microscopy (Difco). Rats were bled 1 week after the second booster injection. Affinity purification of antibodies was performed by coupling the Mice were perfused intracardially with about 100 ml of PBS per GST-fusion proteins to CNBr-activated Sepharose (GE Healthcare UK mouse, which was followed by about 200 ml of 4% paraformalde- Ltd., Buckinghamshire, England) according to the instructions from hyde per mouse. Skin was fixed in 2% glutaraldehyde plus 2% the manufacture. Rat sera prepared from the final bleeds were formaldehyde in cacodylate buffer (0.05 M cacodylate) for 2 h. incubated with each Sepharose-fusion protein complex for 24 h at These samples were rinsed in cacodylate buffer, postfixed in 2% 4 8C and then the complex was washed with phosphate-buffered osmium tetroxide in cacodylate buffer containing 0.5% of potassi- saline (PBS). Then bound antibodies were eluted with 200 mM um ferrocyanide for 2 h and rinsed again in this buffer. Then, glycine–HCl (pH 2.3), which was then neutralized immediately with samples were dehydrated in a graded ethanol series, as described 1 M Tris–HCl (pH 7.4). We confirmed that the antibodies, which we above, embedded in epoxy-resin (LX112; Ladd Research, Burling- used in this study, were specific against EPPK using western blotting. ton, VT, USA), and cut into ultrathin sections (50–70 nm thickness). Sections were placed on copper grids, counterstained with uranyl 2.2. Generation of model wounds acetate and lead citrate, and examined under a transmission electron microscope (JEM-1200EX II, JEOL, Tokyo, Japan) operated Mice were anesthetized with an intraperitoneal injection of at 80 kV. Diameters of keratin filaments were measured on ketamine and xylazine, as described elsewhere [6]. The dorsal electron micrographs of samples from six wild-type and six EPPKÀ/ surface was shaved, and a disposable skin-punch biopsy tool of À mice; 250 filaments were measured in each case. 0.6 cm in diameter (Health Link, Jacksonville, FL, USA) was used to create a full-thickness excision wound that extended to the fascia, 2.5. Double immunostaining and subsequent electron microscopy as described previously [6]. Mice were perfused intracardially as described above and skin 2.3. Histology and immunohistochemistry was fixed in 4% paraformaldehyde for 2 h, and then dehydrated in a graded ethanol series, as described above, and embedded in LR Mice were perfused intracardially with about 100 ml of PBS per White resin (London Resin, Basingstoke, UK). Ultrathin sections mouse, which was followed by about 200 ml of 4% paraformalde- (100–120 nm thickness) were cut with an ultramicrotome and hyde per mouse. Skin was fixed in 4% paraformaldehydes, washed mounted on gold grids. Sections were incubated with the primary in PBS (pH 7.4) and then dehydrated by passage through an ethanol antibodies described above plus 1% BSA for 1 h. After rinsing in PBS, series (50%, 70%, 80%, 95% and twice 100%). After embedding in sections were incubated with EM antibodies raised in goat against paraffin block, 6-mm sections were cut on slides, deparaffinized rat IgG: 15 nm Gold, EM antibodies raised in goat against rabbit and stained with hematoxylin and eosin. IgG: 5 nm Gold, and EM antibodies raised in goat against mouse For immunohistochemical staining, skin was fixed and sec- IgG: 5 nm Gold (BB International, Cardiff, UK), and then rinsed with tioned as described above. All sections were blocked with 3% (w/v) PBS and with distilled water. The immunolabeled sections were bovine serum albumin (BSA) for 30 min. Sections were incubated stained with a saturated solution of uranyl acetate containing lead with primary antibodies for 1 h at room temperature, rinsed with citrate in distilled water.
Load more

Recommended publications
  • Plakins, a Versatile Family of Cytolinkers: Roles in Skin Integrity and in Human Diseases Jamal-Eddine Bouameur1,2, Bertrand Favre1 and Luca Borradori1
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector REVIEW Plakins, a Versatile Family of Cytolinkers: Roles in Skin Integrity and in Human Diseases Jamal-Eddine Bouameur1,2, Bertrand Favre1 and Luca Borradori1 The plakin family consists of giant proteins involved in in (Roper et al., 2002; Jefferson et al., 2004; Sonnenberg and the cross-linking and organization of the cytoskeleton Liem, 2007; Boyer et al., 2010; Suozzi et al., 2012). and adhesion complexes. They further modulate sev- Mammalian plakins share a similar structural organization eral fundamental biological processes, such as cell and comprise seven members: bullous pemphigoid antigen 1 adhesion, migration, and polarization or signaling (BPAG1), desmoplakin, envoplakin, epiplakin, microtubule- pathways. Inherited and acquired defects of plakins actin cross-linking factor 1 (MACF1), periplakin, and plectin in humans and in animal models potentially lead to (Figure 1) (Choi et al., 2002; Jefferson et al., 2007; Choi and dramatic manifestations in the skin, striated muscles, Weis, 2011; Ortega et al., 2011). The existence of develop- and/or nervous system. These observations unequivo- mentally regulated and tissue-specific splice variants of some cally demonstrate the key role of plakins in the plakins further increases the diversity and versatility of these proteins (Table 1; Figure 1; Leung et al., 2001; Rezniczek et al., maintenance of tissue integrity. Here we review the 2003; Lin et al., 2005; Jefferson et al., 2006; Cabral et al., 2010). characteristics of the mammalian plakin members BPAG1 (bullous pemphigoid antigen 1), desmoplakin, PLAKINS IN THE EPIDERMIS plectin, envoplakin, epiplakin, MACF1 (microtubule- Epithelial BPAG1 (BPAG1e, also called BP230) constitutes the actin cross-linking factor 1), and periplakin, highlight- epithelium-specific isoform of BPAG1 and is localized in basal ing their role in skin homeostasis and diseases.
    [Show full text]
  • The Transition from Primary Colorectal Cancer to Isolated Peritoneal Malignancy
    medRxiv preprint doi: https://doi.org/10.1101/2020.02.24.20027318; this version posted February 25, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . The transition from primary colorectal cancer to isolated peritoneal malignancy is associated with a hypermutant, hypermethylated state Sally Hallam1, Joanne Stockton1, Claire Bryer1, Celina Whalley1, Valerie Pestinger1, Haney Youssef1, Andrew D Beggs1 1 = Surgical Research Laboratory, Institute of Cancer & Genomic Science, University of Birmingham, B15 2TT. Correspondence to: Andrew Beggs, [email protected] KEYWORDS: Colorectal cancer, peritoneal metastasis ABBREVIATIONS: Colorectal cancer (CRC), Colorectal peritoneal metastasis (CPM), Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS & HIPEC), Disease free survival (DFS), Differentially methylated regions (DMR), Overall survival (OS), TableFormalin fixed paraffin embedded (FFPE), Hepatocellular carcinoma (HCC) ARTICLE CATEGORY: Research article NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. 1 medRxiv preprint doi: https://doi.org/10.1101/2020.02.24.20027318; this version posted February 25, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . NOVELTY AND IMPACT: Colorectal peritoneal metastasis (CPM) are associated with limited and variable survival despite patient selection using known prognostic factors and optimal currently available treatments.
    [Show full text]
  • Bioinformatics Analysis of Potential Key Genes and Mechanisms in Type 2 Diabetes Mellitus Basavaraj Vastrad1, Chanabasayya Vastrad*2
    bioRxiv preprint doi: https://doi.org/10.1101/2021.03.28.437386; this version posted March 29, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Bioinformatics analysis of potential key genes and mechanisms in type 2 diabetes mellitus Basavaraj Vastrad1, Chanabasayya Vastrad*2 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karnataka, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2021.03.28.437386; this version posted March 29, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Type 2 diabetes mellitus (T2DM) is etiologically related to metabolic disorder. The aim of our study was to screen out candidate genes of T2DM and to elucidate the underlying molecular mechanisms by bioinformatics methods. Expression profiling by high throughput sequencing data of GSE154126 was downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between T2DM and normal control were identified. And then, functional enrichment analyses of gene ontology (GO) and REACTOME pathway analysis was performed. Protein–protein interaction (PPI) network and module analyses were performed based on the DEGs. Additionally, potential miRNAs of hub genes were predicted by miRNet database . Transcription factors (TFs) of hub genes were detected by NetworkAnalyst database. Further, validations were performed by receiver operating characteristic curve (ROC) analysis and real-time polymerase chain reaction (RT-PCR).
    [Show full text]
  • Supplementary Information
    Supplementary information Supplementary Discussion Radiation therapy is one of the key modalities in the management of HNSCC. As of today about 75% of patients with HNSCC are treated with radiotherapy alone or in adjuvant setting after surgery (1). Nevertheless, only few biological parameters have been identified so far as potent prognostic biomarkers for radiotherapy outcome and as potential targets for personalized treatment approaches of radiotherapy combined with targeted drugs. Markers for radiosensitivity include HPV positivity, which has been associated with improved survival and loco-regional control (2-4). On the other hand, tumor volume, the number and intrinsic radioresistance of CSC as well as tumor hypoxia and repopulation were shown to be associated with tumor radioresistance (2, 5- 12) . The tumor growth is maintained by a population of CSC which have unlimited self- renewal potential and cause tumor recurrence if not eradicated by treatment. The number of CSC is a promising biomarker for local tumor control especially for the primary RCTx setting when the number of CSC correlates with primary tumor volumes (8, 9). The tumor suppressor p53 is a key regulator of energy metabolism (13). Mutations in p53 are ubiquitous in HPV negative HNSCC (14). Cal33 HNSCC cells, which were used for the SLC3A2 gene knockout, harbour a p53R175H mutation, which has oncogenic functions and promotes tumor progression (15). A recent study showed that inducible expression of p53R175H in tumor cells increases mitochondrial oxygen consumption and cell proliferation as well as decreasing intracellular ROS levels (16). Interestingly, previous studies demonstrated that the p53R175H mutation prevents cell 1 cycle arrest and apoptosis by attenuation of the expression of stress related gene ATF3 (17, 18).
    [Show full text]
  • Cytoskeleton Structure and Dynamic Behaviour: Quick Excursus from Basic Molecular Mechanisms to Some Implications in Cancer Chemotherapy
    European Review for Medical and Pharmacological Sciences 2009; 13: 13-21 Cytoskeleton structure and dynamic behaviour: quick excursus from basic molecular mechanisms to some implications in cancer chemotherapy C. ALBERTI L.D. of Surgical Semeiotics, University of Parma (Italy) Abstract. – Novel nanoscale microscopic duced tumor cell implantation within surgical technologies are driving dramatic advances in wounds may be prevented by perioperative ad- the knowledge of cytoskeleton structure and dy- ministration of microtubule/actin inhibitors. namics. Cytoskeleton, that is organized into mi- Even though, among the different cancer thera- crotubules, actin meshwork and intermediate fil- py strategies, the chemotherapy could appear to aments, besides providing cells with important be conceptually outclassed because of its low mechanical properties, allows, within the cell, cancer cell-selectivity in comparison with novel not only the molecule cargo transport, but also molecular mechanism-based agents. However the charged particle/biophoton transmission, so "combo-strategies", that combine the chemo- that the cell signaling might be considered as therapeutic high killing potential with new mole- consisting of both molecule/chemically- and cule targeted agents, may be an effective cura- charged particle/physically-addressed systems. tive measure. Some anticytoskeleton agents are Molecular motors that drive molecule cargo under evaluation for their applications in tumor translocation along the cytoskeletal highway, ei- chemotherapy; benomyl, griseofulvin, sulfon- ther through endocytic or secretory-exocytic amides, that are used as antimycotic and antimi- mechanisms, include kinesin and cytoplasmic crobial drugs, appear to have a powerful antitu- dynein, traveling on microtubule, and myosin mor potential by targeting microtubule assembly family members, traveling along actin mesh- dinamics, together with exhibiting, in compari- work.
    [Show full text]
  • Cytoskeletal Proteins in Neurological Disorders
    cells Review Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders Diana C. Muñoz-Lasso 1 , Carlos Romá-Mateo 2,3,4, Federico V. Pallardó 2,3,4 and Pilar Gonzalez-Cabo 2,3,4,* 1 Department of Oncogenomics, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands; [email protected] 2 Department of Physiology, Faculty of Medicine and Dentistry. University of Valencia-INCLIVA, 46010 Valencia, Spain; [email protected] (C.R.-M.); [email protected] (F.V.P.) 3 CIBER de Enfermedades Raras (CIBERER), 46010 Valencia, Spain 4 Associated Unit for Rare Diseases INCLIVA-CIPF, 46010 Valencia, Spain * Correspondence: [email protected]; Tel.: +34-963-395-036 Received: 10 December 2019; Accepted: 29 January 2020; Published: 4 February 2020 Abstract: Recent observations related to the structure of the cytoskeleton in neurons and novel cytoskeletal abnormalities involved in the pathophysiology of some neurological diseases are changing our view on the function of the cytoskeletal proteins in the nervous system. These efforts allow a better understanding of the molecular mechanisms underlying neurological diseases and allow us to see beyond our current knowledge for the development of new treatments. The neuronal cytoskeleton can be described as an organelle formed by the three-dimensional lattice of the three main families of filaments: actin filaments, microtubules, and neurofilaments. This organelle organizes well-defined structures within neurons (cell bodies and axons), which allow their proper development and function through life. Here, we will provide an overview of both the basic and novel concepts related to those cytoskeletal proteins, which are emerging as potential targets in the study of the pathophysiological mechanisms underlying neurological disorders.
    [Show full text]
  • Types I and II Keratin Intermediate Filaments
    Downloaded from http://cshperspectives.cshlp.org/ on October 10, 2021 - Published by Cold Spring Harbor Laboratory Press Types I and II Keratin Intermediate Filaments Justin T. Jacob,1 Pierre A. Coulombe,1,2 Raymond Kwan,3 and M. Bishr Omary3,4 1Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205 2Departments of Biological Chemistry, Dermatology, and Oncology, School of Medicine, and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland 21205 3Departments of Molecular & Integrative Physiologyand Medicine, Universityof Michigan, Ann Arbor, Michigan 48109 4VA Ann Arbor Health Care System, Ann Arbor, Michigan 48105 Correspondence: [email protected] SUMMARY Keratins—types I and II—are the intermediate-filament-forming proteins expressed in epithe- lial cells. They are encoded by 54 evolutionarily conserved genes (28 type I, 26 type II) and regulated in a pairwise and tissue type–, differentiation-, and context-dependent manner. Here, we review how keratins serve multiple homeostatic and stress-triggered mechanical and nonmechanical functions, including maintenance of cellular integrity, regulation of cell growth and migration, and protection from apoptosis. These functions are tightly regulated by posttranslational modifications and keratin-associated proteins. Genetically determined alterations in keratin-coding sequences underlie highly penetrant and rare disorders whose pathophysiology reflects cell fragility or altered
    [Show full text]
  • Estrogen-Related Receptor Gamma Promotes Mesenchymal-To-Epithelial Transition and Suppresses Breast Tumor Growth
    Author Manuscript Published OnlineFirst on February 21, 2011; DOI: 10.1158/0008-5472.CAN-10-1315 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Estrogen-Related Receptor gamma promotes mesenchymal-to-epithelial transition and suppresses breast tumor growth Claire Tiraby, Bethany C. Hazen, Marin L. Gantner, and Anastasia Kralli† Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA Running title: ERRγ induces MET and suppresses breast tumor growth Keywords: breast cancer, mesenchymal-to-epithelial transition, estrogen-related receptor, E-cadherin regulation Funded by the California Breast Cancer Research Program (12IB-0010) and the Department of Defense Breast Cancer Research Program (W81XWH-09-1-0327). †Corresponding author: Anastasia Kralli Department of Chemical Physiology The Scripps Research Institute 10550 North Torrey Pines Road La Jolla, CA 92037 Tel. 858 7847287 Fax. 858 7849132 E-mail: [email protected] Downloaded from cancerres.aacrjournals.org on October 1, 2021. © 2011 American Association for Cancer Research. Author Manuscript Published OnlineFirst on February 21, 2011; DOI: 10.1158/0008-5472.CAN-10-1315 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Abstract Estrogen-Related Receptors alpha (ERRα) and gamma (ERRγ) are orphan nuclear receptors implicated in breast cancer that function similarly in the regulation of oxidative metabolism genes. Paradoxically, in clinical studies high levels of ERRα are associated with poor outcomes whereas high levels of ERRγ are associated with a favorable course. Recent studies suggest that ERRα may indeed promote breast tumor growth. The roles of ERRγ in breast cancer progression and how ERRα and ERRγ may differentially affect cancer growth are unclear.
    [Show full text]
  • The Spectrin Superfamily
    Downloaded from http://cshperspectives.cshlp.org/ on October 4, 2021 - Published by Cold Spring Harbor Laboratory Press Cytoskeletal Integrators: The Spectrin Superfamily Ronald K.H. Liem Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York 10032 Correspondence: [email protected] SUMMARY This review discusses the spectrin superfamily of proteins that function to connect cytoskeletal elements to each other, the cell membrane, and the nucleus. The signature domain is the spectrin repeat, a 106–122-amino-acid segment comprising three a-helices. a-actinin is considered to be the ancestral protein and functions to cross-link actin filaments. It then evolved to generate spectrin and dystrophin that function to link the actin cytoskeleton to the cell membrane, as well as the spectraplakins and plakins that link cytoskeletal elements to each other and to junctional complexes. A final class comprises the nesprins, which are able to bind to the nuclear membrane. This review discusses the domain organization of the various spectrin family members, their roles in protein–protein interactions, and their roles in disease, as determined from mutations, and it also describes the functional roles of the family members as determined from null phenotypes. Outline 1 Introduction 5 Spectraplakins and plakins 2 a-actinin 6 Nesprins 3 Spectrins 7 Concluding remarks 4 Dystrophin and utrophin References Editors: Thomas D. Pollard and Robert D. Goldman Additional Perspectives on The Cytoskeleton available at www.cshperspectives.org Copyright # 2016 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a018259 Cite this article as Cold Spring Harb Perspect Biol 2016;8:a018259 1 Downloaded from http://cshperspectives.cshlp.org/ on October 4, 2021 - Published by Cold Spring Harbor Laboratory Press R.K.H.
    [Show full text]
  • Genetic Variation and Functional Analysis of the Cardiomedin Gene
    TECHNISCHE UNIVERSITÄT MÜNCHEN LEHRSTUHL FÜR EXPERIMENTELLE GENETIK Genetic Variation and Functional Analysis of the Cardiomedin Gene Zasie Susanne Schäfer Vollständiger Abdruck der von der Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigten Dissertation. Vorsitzende: Univ.-Prof. A. Schnieke, Ph.D. Prüfer der Dissertation: 1. apl. Prof. Dr. J. Adamski 2. Univ.-Prof. Dr. Dr. H.-R. Fries 3. Univ.-Prof. Dr. Th. Meitinger Die Dissertation wurde am. 31.05.2011 bei der Technischen Universität München eingereicht und durch die Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt am 02.04.2012 angenommen. Table of Contents Table of contents Abbreviations ........................................................................................................................ 7 1. Summary ..........................................................................................................................10 Zusammenfassung ...............................................................................................................11 2. Introduction ......................................................................................................................12 2.1 Genome-wide association studies (GWAS) and post-GWAS functional genomics ......12 2.2 Genetic influences on cardiac repolarization and sudden cardiac death syndrome in GWAS and the chromosome
    [Show full text]
  • Epiplakin Attenuates Experimental Mouse Liver Injury by Chaperoning Keratin Reorganization
    Accepted Manuscript Epiplakin attenuates experimental mouse liver injury by chaperoning keratin reorganization Sandra Szabo, Karl L. Wögenstein, Christoph H. Österreicher, Nurdan Guldiken, Yu Chen, Carina Doler, Gerhard Wiche, Peter Boor, Johannes Haybaeck, Pavel Strnad, Peter Fuchs PII: S0168-8278(15)00012-4 DOI: http://dx.doi.org/10.1016/j.jhep.2015.01.007 Reference: JHEPAT 5509 To appear in: Journal of Hepatology Received Date: 5 September 2014 Revised Date: 8 December 2014 Accepted Date: 5 January 2015 Please cite this article as: Szabo, S., Wögenstein, K.L., Österreicher, C.H., Guldiken, N., Chen, Y., Doler, C., Wiche, G., Boor, P., Haybaeck, J., Strnad, P., Fuchs, P., Epiplakin attenuates experimental mouse liver injury by chaperoning keratin reorganization, Journal of Hepatology (2015), doi: http://dx.doi.org/10.1016/j.jhep.2015.01.007 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1 Epiplakin attenuates experimental mouse liver injury by chaperoning keratin reorganization. Sandra Szabo*1, Karl L. Wögenstein*1, Christoph H. Österreicher2, Nurdan Guldiken3, Yu Chen3, Carina Doler4, Gerhard Wiche1, Peter Boor5, Johannes
    [Show full text]
  • BT-CSC Dznep Treated Up-Regulated Genes Gene Symbol Gene Name M
    BT-CSC DZNep treated up-regulated genes Gene Symbol Gene Name M Value KRTAP19-1 keratin associated protein 19-1 5.091638802 VPS53 vacuolar protein sorting 53 homolog (S. cerevisiae) 4.920143235 HEATR2 HEAT repeat containing 2 4.545255947 BRAF v-raf murine sarcoma viral oncogene homolog B1 4.404531741 PCDH7 protocadherin 7 4.378536321 PRKACB protein kinase, cAMP-dependent, catalytic, beta 4.337185544 C6orf166 chromosome 6 open reading frame 166 4.244909909 HIST1H3H histone cluster 1, H3h 4.085723721 CRAMP1L Crm, cramped-like (Drosophila) 3.811674874 RPS15 ribosomal protein S15 3.776296646 EPPK1 epiplakin 1 3.724368921 LAMA4 laminin, alpha 4 3.634864123 SEMA3C sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3C 3.504490549 MALAT1 metastasis associated lung adenocarcinoma transcript 1 (non-protein coding) 3.3915307 EPC1 enhancer of polycomb homolog 1 (Drosophila) 3.37404925 ANKRD13C ankyrin repeat domain 13C 3.367543301 HIST2H2BE histone cluster 2, H2be 3.331087945 LOC158301 hypothetical protein LOC158301 3.328891352 LOC56755 hypothetical protein LOC56755 3.233203867 HEXIM1 hexamethylene bis-acetamide inducible 1 3.231227044 SYT11 synaptotagmin XI 3.217641148 KRTAP7-1 keratin associated protein 7-1 3.202664068 TEX14 testis expressed 14 3.19144479 TUG1 taurine upregulated gene 1 3.15045817 KLHL28 kelch-like 28 (Drosophila) 3.074070618 KRTAP19-3 keratin associated protein 19-3 3.056583425 DOCK1 dedicator of cytokinesis 1 3.053526521 NHEDC1 Na+/H+ exchanger domain containing 1 3.013610505 SFN stratifin 3.000939496
    [Show full text]