Adenomatous Polyposis Coli (APC) Is Required for Normal Development of Skin and Thymus
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FK506-Binding Protein 12.6/1B, a Negative Regulator of [Ca2+], Rescues Memory and Restores Genomic Regulation in the Hippocampus of Aging Rats
This Accepted Manuscript has not been copyedited and formatted. The final version may differ from this version. A link to any extended data will be provided when the final version is posted online. Research Articles: Neurobiology of Disease FK506-Binding Protein 12.6/1b, a negative regulator of [Ca2+], rescues memory and restores genomic regulation in the hippocampus of aging rats John C. Gant1, Eric M. Blalock1, Kuey-Chu Chen1, Inga Kadish2, Olivier Thibault1, Nada M. Porter1 and Philip W. Landfield1 1Department of Pharmacology & Nutritional Sciences, University of Kentucky, Lexington, KY 40536 2Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294 DOI: 10.1523/JNEUROSCI.2234-17.2017 Received: 7 August 2017 Revised: 10 October 2017 Accepted: 24 November 2017 Published: 18 December 2017 Author contributions: J.C.G. and P.W.L. designed research; J.C.G., E.M.B., K.-c.C., and I.K. performed research; J.C.G., E.M.B., K.-c.C., I.K., and P.W.L. analyzed data; J.C.G., E.M.B., O.T., N.M.P., and P.W.L. wrote the paper. Conflict of Interest: The authors declare no competing financial interests. NIH grants AG004542, AG033649, AG052050, AG037868 and McAlpine Foundation for Neuroscience Research Corresponding author: Philip W. Landfield, [email protected], Department of Pharmacology & Nutritional Sciences, University of Kentucky, 800 Rose Street, UKMC MS 307, Lexington, KY 40536 Cite as: J. Neurosci ; 10.1523/JNEUROSCI.2234-17.2017 Alerts: Sign up at www.jneurosci.org/cgi/alerts to receive customized email alerts when the fully formatted version of this article is published. -
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. -
Genetic Background Effects of Keratin 8 and 18 in a DDC-Induced Hepatotoxicity and Mallory-Denk Body Formation Mouse Model
Laboratory Investigation (2012) 92, 857–867 & 2012 USCAP, Inc All rights reserved 0023-6837/12 $32.00 Genetic background effects of keratin 8 and 18 in a DDC-induced hepatotoxicity and Mallory-Denk body formation mouse model Johannes Haybaeck1, Cornelia Stumptner1, Andrea Thueringer1, Thomas Kolbe2, Thomas M Magin3, Michael Hesse4, Peter Fickert5, Oleksiy Tsybrovskyy1, Heimo Mu¨ller1, Michael Trauner5,6, Kurt Zatloukal1 and Helmut Denk1 Keratin 8 (K8) and keratin 18 (K18) form the major hepatocyte cytoskeleton. We investigated the impact of genetic loss of either K8 or K18 on liver homeostasis under toxic stress with the hypothesis that K8 and K18 exert different functions. krt8À/À and krt18À/À mice crossed into the same 129-ola genetic background were treated by acute and chronic ad- ministration of 3,5-diethoxy-carbonyl-1,4-dihydrocollidine (DDC). In acutely DDC-intoxicated mice, macrovesicular steatosis was more pronounced in krt8À/À and krt18À/À compared with wild-type (wt) animals. Mallory-Denk bodies (MDBs) appeared in krt18À/À mice already at an early stage of intoxication in contrast to krt8À/À mice that did not display MDB formation when fed with DDC. Keratin-deficient mice displayed significantly lower numbers of apoptotic hepatocytes than wt animals. krt8À/À, krt18À/À and control mice displayed comparable cell proliferation rates. Chronically DDC-intoxicated krt18À/À and wt mice showed a similarly increased degree of steatohepatitis with hepatocyte ballooning and MDB formation. In krt8À/À mice, steatosis was less, ballooning, and MDBs were absent. krt18À/À mice developed MDBs whereas krt8À/À mice on the same genetic background did not, highlighting the significance of different structural properties of keratins. -
Genome-Wide Rnai Screening Identifies Human Proteins with A
RESOURCES Genome-wide RNAi screening identifies human proteins with a regulatory function in the early secretory pathway Jeremy C. Simpson1,7, Brigitte Joggerst2, Vibor Laketa2, Fatima Verissimo2, Cihan Cetin2, Holger Erfle2,6, Mariana G. Bexiga1, Vasanth R. Singan1, Jean-Karim Hériché3, Beate Neumann3, Alvaro Mateos2, Jonathon Blake4, Stephanie Bechtel5, Vladimir Benes4, Stefan Wiemann5, Jan Ellenberg2,3 and Rainer Pepperkok2,7 The secretory pathway in mammalian cells has evolved to facilitate the transfer of cargo molecules to internal and cell surface membranes. Use of automated microscopy-based genome-wide RNA interference screens in cultured human cells allowed us to identify 554 proteins influencing secretion. Cloning, fluorescent-tagging and subcellular localization analysis of 179 of these proteins revealed that more than two-thirds localize to either the cytoplasm or membranes of the secretory and endocytic pathways. The depletion of 143 of them resulted in perturbations in the organization of the COPII and/or COPI vesicular coat complexes of the early secretory pathway, or the morphology of the Golgi complex. Network analyses revealed a so far unappreciated link between early secretory pathway function, small GTP-binding protein regulation, actin cytoskeleton organization and EGF-receptor-mediated signalling. This work provides an important resource for an integrative understanding of global cellular organization and regulation of the secretory pathway in mammalian cells. Within higher eukaryotic cells membrane traffic pathways connect the Extensive efforts over many years have revealed a significant number various membrane-bounded organelles, thereby ensuring that they of regulators associated with the secretory pathway. Early biochemical retain the correct complement of proteins and lipids to maintain approaches to identify individual machinery components have started cellular homeostasis. -
Relevance Network Between Chemosensitivity and Transcriptome in Human Hepatoma Cells1
Vol. 2, 199–205, February 2003 Molecular Cancer Therapeutics 199 Relevance Network between Chemosensitivity and Transcriptome in Human Hepatoma Cells1 Masaru Moriyama,2 Yujin Hoshida, topoisomerase II  expression, whereas it negatively Motoyuki Otsuka, ShinIchiro Nishimura, Naoya Kato, correlated with expression of carboxypeptidases A3 Tadashi Goto, Hiroyoshi Taniguchi, and Z. Response to nimustine was associated with Yasushi Shiratori, Naohiko Seki, and Masao Omata expression of superoxide dismutase 2. Department of Gastroenterology, Graduate School of Medicine, Relevance networks identified several negative University of Tokyo, Tokyo 113-8655 [M. M., Y. H., M. O., N. K., T. G., H. T., Y. S., M. O.]; Cellular Informatics Team, Computational Biology correlations between gene expression and resistance, Research Center, Tokyo 135-0064 [S. N.]; and Department of which were missed by hierarchical clustering. Our Functional Genomics, Graduate School of Medicine, Chiba University, results suggested the necessity of systematically Chiba 260-8670 [N. S.], Japan evaluating the transporting systems that may play a major role in resistance in hepatoma. This may provide Abstract useful information to modify anticancer drug action in Generally, hepatoma is not a chemosensitive tumor, hepatoma. and the mechanism of resistance to anticancer drugs is not fully elucidated. We aimed to comprehensively Introduction evaluate the relationship between chemosensitivity and Hepatoma is a major cause of death even in developed gene expression profile in human hepatoma cells, by countries, and its incidence is increasing (1). Despite the using microarray analysis, and analyze the data by progress of therapeutic technique (2), the efficacy of radical constructing relevance networks. therapy is hampered by frequent recurrence and advance of In eight hepatoma cell lines (HLE, HLF, Huh7, Hep3B, the tumor (3). -
Genome-Wide Enrichment Analysis Between Endometriosis and Obesity-Related Traits Reveals Novel Susceptibility Loci
Human Molecular Genetics, 2015, Vol. 24, No. 4 1185–1199 doi:10.1093/hmg/ddu516 Advance Access published on October 8, 2014 Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci Nilufer Rahmioglu1, Stuart Macgregor2, Alexander W. Drong1,A˚ sa K. Hedman1,5, Holly R. Harris6,7, Joshua C. Randall8, Inga Prokopenko1,9,10, The International Endogene Consortium (IEC), The GIANT Consortium, Dale R. Nyholt3, Andrew P. Morris1,11,{, Grant W. Montgomery4,{, Downloaded from https://academic.oup.com/hmg/article/24/4/1185/617584 by guest on 05 February 2021 Stacey A. Missmer6,{, Cecilia M. Lindgren1,12,{ and Krina T. Zondervan1,13,∗,{ 1Wellcome Trust Center for Human Genetics, University of Oxford, Oxford OX3 7BN, UK, 2Statistical Genetics, 3Neurogenetics, 4Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia, 5Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden, 6Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA, 7Unit of Nutritional Epidemiology, Institute for Environmental Medicine, Karolinska Institutet, PO Box 210, SE-171 77 Stockholm, Sweden, 8Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK, 9Department of Genomics of Common Disease, Imperial College London, London W12 0NN, UK, 10Oxford Centre for Diabetes, Endocrinology and Metabolism, University -
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. -
Identification of Trichoplein, a Novel Keratin Filament- Binding Protein
Research Article 1081 Identification of trichoplein, a novel keratin filament- binding protein Miwako Nishizawa1,*, Ichiro Izawa1,*, Akihito Inoko1,*, Yuko Hayashi1, Koh-ichi Nagata1, Tomoya Yokoyama1,2, Jiro Usukura3 and Masaki Inagaki1,‡ 1Division of Biochemistry, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan 2Department of Dermatology, Mie University Faculty of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan 3Department of Anatomy and Cell Biology, Nagoya University School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan *These authors contributed equally to this work ‡Author for correspondence (e-mail: [email protected]) Accepted 29 November 2004 Journal of Cell Science 118, 1081-1090 Published by The Company of Biologists 2005 doi:10.1242/jcs.01667 Summary Keratins 8 and 18 (K8/18) are major components of the antibody in a complex with K8/18 and immunostaining intermediate filaments (IFs) of simple epithelia. We report revealed that trichoplein colocalized with K8/18 filaments here the identification of a novel protein termed in HeLa cells. In polarized Caco-2 cells, trichoplein trichoplein. This protein shows a low degree of sequence colocalized not only with K8/18 filaments in the apical similarity to trichohyalin, plectin and myosin heavy chain, region but also with desmoplakin, a constituent of and is a K8/18-binding protein. Among interactions desmosomes. In the absorptive cells of the small intestine, between trichoplein and various IF proteins that we trichoplein colocalized with K8/18 filaments at the apical tested using two-hybrid methods, trichoplein interacted cortical region, and was also concentrated at desmosomes. -
The Abundance of Cis-Acting Loci Leading to Differential Allele
Yeo et al. BMC Genomics (2016) 17:620 DOI 10.1186/s12864-016-2922-9 RESEARCH ARTICLE Open Access The abundance of cis-acting loci leading to differential allele expression in F1 mice and their relationship to loci harboring genes affecting complex traits Seungeun Yeo1, Colin A. Hodgkinson1, Zhifeng Zhou1, Jeesun Jung2, Ming Leung1, Qiaoping Yuan1 and David Goldman1* Abstract Background: Genome-wide surveys have detected cis-acting quantitative trait loci altering levels of RNA transcripts (RNA-eQTLs) by associating SNV alleles to transcript levels. However, the sensitivity and specificity of detection of cis- expression quantitative trait loci (eQTLs) by genetic approaches, reliant as it is on measurements of transcript levels in recombinant inbred strains or offspring from arranged crosses, is unknown, as is their relationship to QTL’s for complex phenotypes. Results: We used transcriptome-wide differential allele expression (DAE) to detect cis-eQTLs in forebrain and kidney from reciprocal crosses between three mouse inbred strains, 129S1/SvlmJ, DBA/2J, and CAST/EiJ and C57BL/6 J. Two of these crosses were previously characterized for cis-eQTLs and QTLs for various complex phenotypes by genetic analysis of recombinant inbred (RI) strains. 5.4 %, 1.9 % and 1.5 % of genes assayed in forebrain of B6/ 129SF1, B6/DBAF1, and B6/CASTF1 mice, respectively, showed differential allelic expression, indicative of cis-acting alleles at these genes. Moreover, the majority of DAE QTLs were observed to be tissue-specific with only a small fraction showing cis-effects in both tissues. Comparing DAE QTLs in F1 mice to cis-eQTLs previously mapped in RI strains we observed that many of the cis-eQTLs were not confirmed by DAE. -
Keratins Couple with the Nuclear Lamina and Regulate Proliferation in Colonic Epithelial Cells Carl-Gustaf A
bioRxiv preprint doi: https://doi.org/10.1101/2020.06.22.164467; this version posted June 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Keratins couple with the nuclear lamina and regulate proliferation in colonic epithelial cells Carl-Gustaf A. Stenvall1*, Joel H. Nyström1*, Ciarán Butler-Hallissey1,5, Stephen A. Adam2, Roland Foisner3, Karen M. Ridge2, Robert D. Goldman2, Diana M. Toivola1,4 1 Cell Biology, Biosciences, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland 2 Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA 3 Max Perutz Labs, Medical University of Vienna, Vienna Biocenter Campus (VBC), Vienna, Austria 4 Turku Center for Disease Modeling, Turku, Finland 5 Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland * indicates equal contribution Running Head: Colonocyte keratins couple to nuclear lamina Corresponding author: Diana M. Toivola Cell Biology/Biosciences, Faculty of Science and Engineering, Åbo Akademi University Tykistökatu 6A, FIN-20520 Turku, Finland Telephone: +358 2 2154092 E-mail: [email protected] Keywords: Keratins, lamin, intermediate filament, colon epithelial cells, LINC proteins, proliferation, pRb, YAP bioRxiv preprint doi: https://doi.org/10.1101/2020.06.22.164467; this version posted June 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
A Functional Enrichment Test for Molecular Convergent Evolution Finds a Clear Protein-Coding Signal in Echolocating Bats and Whales
A functional enrichment test for molecular convergent evolution finds a clear protein-coding signal in echolocating bats and whales Amir Marcovitza,1, Yatish Turakhiab,1, Heidi I. Chena,1, Michael Gloudemansc, Benjamin A. Braund, Haoqing Wange, and Gill Bejeranoa,d,f,g,2 aDepartment of Developmental Biology, Stanford University, Stanford, CA 94305; bDepartment of Electrical Engineering, Stanford University, Stanford, CA 94305; cBiomedical Informatics Program, Stanford University, Stanford, CA 94305; dDepartment of Computer Science, Stanford University, Stanford, CA 94305; eDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305; fDepartment of Pediatrics, Stanford University, Stanford, CA 94305; and gDepartment of Biomedical Data Science, Stanford University, Stanford, CA 94305 Edited by Scott V. Edwards, Harvard University, Cambridge, MA, and approved September 3, 2019 (received for review November 2, 2018) Distantly related species entering similar biological niches often parallel shifts in evolutionary rates in independent lineages of adapt by evolving similar morphological and physiological char- aquatic mammals (15). However, later analyses demonstrated that acters. How much genomic molecular convergence (particularly of the genome-wide frequency of molecular convergence in echolocating highly constrained coding sequence) contributes to convergent mammals is similar to the frequency in nonecholocating control phenotypic evolution, such as echolocation in bats and whales, is a outgroups, -
Pflugers Final
CORE Metadata, citation and similar papers at core.ac.uk Provided by Serveur académique lausannois A comprehensive analysis of gene expression profiles in distal parts of the mouse renal tubule. Sylvain Pradervand2, Annie Mercier Zuber1, Gabriel Centeno1, Olivier Bonny1,3,4 and Dmitri Firsov1,4 1 - Department of Pharmacology and Toxicology, University of Lausanne, 1005 Lausanne, Switzerland 2 - DNA Array Facility, University of Lausanne, 1015 Lausanne, Switzerland 3 - Service of Nephrology, Lausanne University Hospital, 1005 Lausanne, Switzerland 4 – these two authors have equally contributed to the study to whom correspondence should be addressed: Dmitri FIRSOV Department of Pharmacology and Toxicology, University of Lausanne, 27 rue du Bugnon, 1005 Lausanne, Switzerland Phone: ++ 41-216925406 Fax: ++ 41-216925355 e-mail: [email protected] and Olivier BONNY Department of Pharmacology and Toxicology, University of Lausanne, 27 rue du Bugnon, 1005 Lausanne, Switzerland Phone: ++ 41-216925417 Fax: ++ 41-216925355 e-mail: [email protected] 1 Abstract The distal parts of the renal tubule play a critical role in maintaining homeostasis of extracellular fluids. In this review, we present an in-depth analysis of microarray-based gene expression profiles available for microdissected mouse distal nephron segments, i.e., the distal convoluted tubule (DCT) and the connecting tubule (CNT), and for the cortical portion of the collecting duct (CCD) (Zuber et al., 2009). Classification of expressed transcripts in 14 major functional gene categories demonstrated that all principal proteins involved in maintaining of salt and water balance are represented by highly abundant transcripts. However, a significant number of transcripts belonging, for instance, to categories of G protein-coupled receptors (GPCR) or serine-threonine kinases exhibit high expression levels but remain unassigned to a specific renal function.