DOCSLIB.ORG

Centre for Arab Genomic Studies a Division of Sheikh Hamdan Award for Medical Sciences

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Centre for Arab Genomic Studies a Division of Sheikh Hamdan Award for Medical Sciences Centre for Arab Genomic Studies A Division of Sheikh Hamdan Award for Medical Sciences The atalogue for ransmission enetics in rabs C T G A CTGA Database ATP/GTP-Binding Protein 1 Alternative Names cells. Analysis of pcd mice has shown increased AGTPBP1 levels of tubulin polyglutamylation in the brain. Nervous System Nuclear Protein Induced by Axotomy Molecular Genetics NNA1 The AGTPBP1 gene is located on the long arm of KIAA1035 chromosome 9 at position 9q21.33. The gene spans Cytosolic Carboxypeptidase 1 a length of 195.4 kb of DNA and its coding CCP1 sequence is spread across 31 exons. Several additional isoforms of the AGTPBP1 gene exist due Record Category to alternatively spliced transcript variants. While Gene locus the gene is widely expressed in the human body, overexpression is seen in the fetal brain, retina and WHO-ICD peripheral blood mononuclear cells. N/A to gene loci Epidemiology in the Arab World Incidence per 100,000 Live Births Saudi Arabia N/A to gene loci Monies et al. (2017) analyzed the findings of 1000 diagnostic panels and exomes carried out at a next OMIM Number generation sequencing lab in Saudi Arabia. One 606830 patient, a 2-year-old female, presented with congenital hypotonia and global developmental Mode of Inheritance delay. She was found to suffer from diffuse N/A to gene loci atrophic changes of the brain indicated by diminished myelinated white matter volume, Gene Map Locus deepened sulci, dilated ventricular system, thinned 9q21.33 corpus callosum, increased mamillo-potine distance and significantly prominent extra axial CSF spaces. Description Using WES, a homozygous mutation (c.2908C>T, The AGTPBP1 gene, also known as CCP1, encodes p.R970W) was identified in exon 20 of the patient’s a zinc carboxypeptidase enzyme that is responsible AGTPBP1 gene. This gene mutation was for catalysing the deglutamylation of target considered a candidate for pathogenicity as it was a proteins. CCP1 can carry out the deglutamylation of novel variant located within the autozygome that polyglutamate side chains added by post- was predicted to be deleterious, and mutations in translational modification to the C-termini of the mouse orthologue of the AGTPBP1 gene have tubulin proteins. It can also mediate the been shown to result in cerebellar Purkinje neuron deglutamylation of gene-encoded polyglutamates degeneration. The authors noted that further studies from proteins such as MYLK. are required to independently confirm this association. Mouse models have helped elucidate the physiological role of CCP1. The mouse orthologue References gene, Ccp1, is found to be mutated in the Purkinje Monies D, Abouelhoda M, AlSayed M, Alhassnan cell degeneration (pcd) phenotype of mice. These Z, Alotaibi M, Kayyali H, Al-Owain M, Shah A, pcd mice exhibit ataxia subsequent to cerebellar Rahbeeni Z, Al-Muhaizea MA, Alzaidan HI, Purkinje cell degeneration. They also suffer the Cupler E, Bohlega S, Faqeih E, Faden M, Alyounes progressive deterioration of thalamic neurons, B, Jaroudi D, Goljan E, Elbardisy H, Akilan A, retinal photoreceptors and olfactory bulb mitral Albar R, Aldhalaan H, Gulab S, Chedrawi A, Al Saud BK, Kurdi W, Makhseed N, Alqasim T, El Copyright © Centre for Arab Genomic Studies 1 Khashab HY, Al-Mousa H, Alhashem A, Kanaan I, Alfadhel M, Faquih T, El-Kalioby M, Subhani S, Algoufi T, Alsaleem K, Basha TA, Al-Murshedi F, Shah Z, Moghrabi N, Meyer BF, Alkuraya FS. The Khan S, Al-Kindy A, Alnemer M, Al-Hajjar S, landscape of genetic diseases in Saudi Arabia based Alyamani S, Aldhekri H, Al-Mehaidib A, Arnaout on the first 1000 diagnostic panels and exomes. R, Dabbagh O, Shagrani M, Broering D, Tulbah M, Hum Genet. 2017 Aug;136(8):921-939. PMID: Alqassmi A, Almugbel M, AlQuaiz M, Alsaman A, 28600779. Al-Thihli K, Sulaiman RA, Al-Dekhail W, Alsaegh A, Bashiri FA, Qari A, Alhomadi S, Alkuraya H, Related CTGA Records Alsebayel M, Hamad MH, Szonyi L, Abaalkhail F, Al-Mayouf SM, Almojalli H, Alqadi KS, Elsiesy H, External Links Shuaib TM, Seidahmed MZ, Abosoudah I, Akleh http://www.genecards.org/cgi- H, AlGhonaium A, Alkharfy TM, Al Mutairi F, bin/carddisp.pl?gene=AGTPBP1 Eyaid W, Alshanbary A, Sheikh FR, Alsohaibani FI, Alsonbul A, Al Tala S, Balkhy S, Bassiouni R, Contributors Alenizi AS, Hussein MH, Hassan S, Khalil M, Sayeeda Hana Tabarki B, Alshahwan S, Oshi A, Sabr Y, 03.08.2017 Alsaadoun S, Salih MA, Mohamed S, Sultana H, Tamim A, El-Haj M, Alshahrani S, Bubshait DK, Copyright © Centre for Arab Genomic Studies 2 .
Load more

Recommended publications
  • Primate Specific Retrotransposons, Svas, in the Evolution of Networks That Alter Brain Function
    Title: Primate specific retrotransposons, SVAs, in the evolution of networks that alter brain function. Olga Vasieva1*, Sultan Cetiner1, Abigail Savage2, Gerald G. Schumann3, Vivien J Bubb2, John P Quinn2*, 1 Institute of Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, U.K 2 Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, The University of Liverpool, Liverpool L69 3BX, UK 3 Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, D-63225 Germany *. Corresponding author Olga Vasieva: Institute of Integrative Biology, Department of Comparative genomics, University of Liverpool, Liverpool, L69 7ZB, [email protected] ; Tel: (+44) 151 795 4456; FAX:(+44) 151 795 4406 John Quinn: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, The University of Liverpool, Liverpool L69 3BX, UK, [email protected]; Tel: (+44) 151 794 5498. Key words: SVA, trans-mobilisation, behaviour, brain, evolution, psychiatric disorders 1 Abstract The hominid-specific non-LTR retrotransposon termed SINE–VNTR–Alu (SVA) is the youngest of the transposable elements in the human genome. The propagation of the most ancient SVA type A took place about 13.5 Myrs ago, and the youngest SVA types appeared in the human genome after the chimpanzee divergence. Functional enrichment analysis of genes associated with SVA insertions demonstrated their strong link to multiple ontological categories attributed to brain function and the disorders. SVA types that expanded their presence in the human genome at different stages of hominoid life history were also associated with progressively evolving behavioural features that indicated a potential impact of SVA propagation on a cognitive ability of a modern human.
    [Show full text]
  • Mitoxplorer, a Visual Data Mining Platform To
    mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dynamics and mutations Annie Yim, Prasanna Koti, Adrien Bonnard, Fabio Marchiano, Milena Dürrbaum, Cecilia Garcia-Perez, José Villaveces, Salma Gamal, Giovanni Cardone, Fabiana Perocchi, et al. To cite this version: Annie Yim, Prasanna Koti, Adrien Bonnard, Fabio Marchiano, Milena Dürrbaum, et al.. mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dy- namics and mutations. Nucleic Acids Research, Oxford University Press, 2020, 10.1093/nar/gkz1128. hal-02394433 HAL Id: hal-02394433 https://hal-amu.archives-ouvertes.fr/hal-02394433 Submitted on 4 Dec 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License Nucleic Acids Research, 2019 1 doi: 10.1093/nar/gkz1128 Downloaded from https://academic.oup.com/nar/advance-article-abstract/doi/10.1093/nar/gkz1128/5651332 by Bibliothèque de l'université la Méditerranée user on 04 December 2019 mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dynamics and mutations Annie Yim1,†, Prasanna Koti1,†, Adrien Bonnard2, Fabio Marchiano3, Milena Durrbaum¨ 1, Cecilia Garcia-Perez4, Jose Villaveces1, Salma Gamal1, Giovanni Cardone1, Fabiana Perocchi4, Zuzana Storchova1,5 and Bianca H.
    [Show full text]
  • Avian Binocularity and Adaptation to Nocturnal Environments: Genomic Insights Froma Highly Derived Visual Phenotype Rui Borges Universidade Do Porto - Portugal
    Nova Southeastern University NSUWorks Biology Faculty Articles Department of Biological Sciences 8-22-2019 Avian Binocularity and Adaptation to Nocturnal Environments: Genomic Insights froma Highly Derived Visual Phenotype Rui Borges Universidade do Porto - Portugal Joao Fonseca Universidade do Porto - Portugal Cidalia Gomes Universidade do Porto - Portugal Warren E. Johnson Smithsonian Institution Stephen James O'Brien St. Petersburg State University - Russia; Nova Southeastern University, [email protected] See next page for additional authors Follow this and additional works at: https://nsuworks.nova.edu/cnso_bio_facarticles Part of the Biology Commons NSUWorks Citation Borges, Rui; Joao Fonseca; Cidalia Gomes; Warren E. Johnson; Stephen James O'Brien; Guojie Zhang; M. Thomas P. Gilbert; Erich D. Jarvis; and Agostinho Antunes. 2019. "Avian Binocularity and Adaptation to Nocturnal Environments: Genomic Insights froma Highly Derived Visual Phenotype." Genome Biology and Evolution 11, (8): 2244-2255. doi:10.1093/gbe/evz111. This Article is brought to you for free and open access by the Department of Biological Sciences at NSUWorks. It has been accepted for inclusion in Biology Faculty Articles by an authorized administrator of NSUWorks. For more information, please contact [email protected]. Authors Rui Borges, Joao Fonseca, Cidalia Gomes, Warren E. Johnson, Stephen James O'Brien, Guojie Zhang, M. Thomas P. Gilbert, Erich D. Jarvis, and Agostinho Antunes This article is available at NSUWorks: https://nsuworks.nova.edu/cnso_bio_facarticles/982 GBE Avian Binocularity and Adaptation to Nocturnal Environments: Genomic Insights from a Highly Derived Visual Downloaded from https://academic.oup.com/gbe/article-abstract/11/8/2244/5544263 by Nova Southeastern University/HPD Library user on 16 September 2019 Phenotype Rui Borges1,2,Joao~ Fonseca1,Cidalia Gomes1, Warren E.
    [Show full text]
  • Viewed and Published Immediately Upon Acceptance Cited in Pubmed and Archived on Pubmed Central Yours — You Keep the Copyright
    BMC Genomics BioMed Central Research article Open Access Differential gene expression in ADAM10 and mutant ADAM10 transgenic mice Claudia Prinzen1, Dietrich Trümbach2, Wolfgang Wurst2, Kristina Endres1, Rolf Postina1 and Falk Fahrenholz*1 Address: 1Johannes Gutenberg-University, Institute of Biochemistry, Mainz, Johann-Joachim-Becherweg 30, 55128 Mainz, Germany and 2Helmholtz Zentrum München – German Research Center for Environmental Health, Institute for Developmental Genetics, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany Email: Claudia Prinzen - [email protected]; Dietrich Trümbach - [email protected]; Wolfgang Wurst - [email protected]; Kristina Endres - [email protected]; Rolf Postina - [email protected]; Falk Fahrenholz* - [email protected] * Corresponding author Published: 5 February 2009 Received: 19 June 2008 Accepted: 5 February 2009 BMC Genomics 2009, 10:66 doi:10.1186/1471-2164-10-66 This article is available from: http://www.biomedcentral.com/1471-2164/10/66 © 2009 Prinzen et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: In a transgenic mouse model of Alzheimer disease (AD), cleavage of the amyloid precursor protein (APP) by the α-secretase ADAM10 prevented amyloid plaque formation, and alleviated cognitive deficits. Furthermore, ADAM10 overexpression increased the cortical synaptogenesis. These results suggest that upregulation of ADAM10 in the brain has beneficial effects on AD pathology. Results: To assess the influence of ADAM10 on the gene expression profile in the brain, we performed a microarray analysis using RNA isolated from brains of five months old mice overexpressing either the α-secretase ADAM10, or a dominant-negative mutant (dn) of this enzyme.
    [Show full text]
  • Viewed, and Verify Tissue Integrity and Assure the Success of the Per- Digital Scans Were Recorded Using a Zeiss 510 Multi-Pho- Fusion
    Molecular Brain BioMed Central Research Open Access Autophagy activation and enhanced mitophagy characterize the Purkinje cells of pcd mice prior to neuronal death Lisa Chakrabarti1, Jeremiah Eng1, Nishi Ivanov2, Gwenn A Garden2,4 and Albert R La Spada*1,2,3,4,5 Address: 1Department of Laboratory Medicine, University of Washington, Seattle, WA, USA, 2Department of Neurology, University of Washington, Seattle, WA, USA, 3Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA, 4Center for Neurogenetics & Neurotherapeutics, University of Washington, Seattle, WA, USA and 5Departments of Pediatrics and Cellular & Molecular Medicine, University of California, San Diego, USA Email: Lisa Chakrabarti - [email protected]; Jeremiah Eng - [email protected]; Nishi Ivanov - [email protected]; Gwenn A Garden - [email protected]; Albert R La Spada* - [email protected] * Corresponding author Published: 29 July 2009 Received: 30 May 2009 Accepted: 29 July 2009 Molecular Brain 2009, 2:24 doi:10.1186/1756-6606-2-24 This article is available from: http://www.molecularbrain.com/content/2/1/24 © 2009 Chakrabarti et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Purkinje cells are a class of specialized neurons in the cerebellum, and are among the most metabolically active of all neurons, as they receive immense synaptic stimulation, and provide the only efferent output from the cerebellum. Degeneration of Purkinje cells is a common feature of inherited ataxias in humans and mice.
    [Show full text]
  • Datasheet Blank Template
    SAN TA C RUZ BI OTEC HNOL OG Y, INC . AGTPBP1 (S-14): sc-162500 BACKGROUND PRODUCT AGTPBP1 (ATP/GTP-binding protein 1), also known as CCP1 (cytosolic car - Each vial contains 200 µg IgG in 1.0 ml of PBS with < 0.1% sodium azide boxypeptidase 1), KIAA1035 or NNA1, is a 1,226 amino acid protein that be- and 0.1% gelatin. longs to the peptidase M14 family. AGTPBP1 contains an ATP/GTP-binding Blocking peptide available for competition studies, sc-162500 P, (100 µg motif of the P-loop type, a leucine zipper, a nuclear localization signal, a zinc pep tide in 0.5 ml PBS containing < 0.1% sodium azide and 0.2% BSA). carboxypeptidase signature and a nucleotide-binding site. Expressed at high levels in testis, heart and dorsal root ganglia and at lower levels in skeletal APPLICATIONS muscle and kidney, AGTPBP1 may be responsible for Purkinje cell degenera - tion (pcd). The loss of AGTPBP1 in Purkinje cells leads directly to their degen - AGTPBP1 (S-14) is recommended for detection of AGTPBP1 of mouse, rat eration and a functional carboxypeptidase domain is crucial for AGTPBP1 to and human origin by Western Blotting (starting dilution 1:200, dilution range support neuron survival. Two isoforms exists due to alternative splicing events. 1:100-1:1000), immunofluorescence (starting dilution 1:50, dilution range 1:50-1:500) and solid phase ELISA (starting dilution 1:30, dilution range REFERENCES 1:30- 1:3000). 1. Harris, A., et al. 2000. Regenerating motor neurons express Nna1, a AGTPBP1 (S-14) is also recommended for detection of AGTPBP1 in additional novel ATP/GTP-binding protein related to zinc carboxypeptidases.
    [Show full text]
  • Jan Evangelista Purkyně and the Cerebellum Then and Now
    Physiol. Res. 64 (Suppl. 5): S567-S584, 2015 https://doi.org/10.33549/physiolres.933231 REVIEW Jan Evangelista Purkyně and the Cerebellum Then and Now F. VOŽEH1,2 1Department of Pathophysiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic, 2Laboratory of Neurodegenerative Disorders, Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic Received March 31, 2015 Accepted June 25, 2015 On-line December 15, 2015 Summary Introduction The name of Jan Evangelista Purkyně and the cerebellum belong inseparably together. He was the first who saw and described the Jan Evangelista Purkyně was the most largest nerve cells in the brain, de facto in the cerebellum. The formidable figure in Czech physiology on the world who most distinguished researchers of the nervous system then brought many scientific discoveries into the biological, showed him the highest recognition by naming these neurons as physiological and biomedical sciences. Among the Purkinje cells. Through experiments by J. E. Purkyně and his systems to which he paid attention it was mainly the followers properly functionally was attributed to the cerebellum nervous system and especially the cerebellum. J. E. share in precision of motor skills. Despite ongoing and fruitful Purkyně was the first scientist to see and describe the research, after a relatively long time, especially in the last two largest nerve cells in the brain, de facto in the cerebellum. decades, scientists had to constantly replenish and re-evaluate He hand-illustrated them at his memorable lecture to the the traditional conception of the cerebellum and formulate a new professional public in Prague in 1837.
    [Show full text]
  • 1 Novel Expression Signatures Identified by Transcriptional Analysis
    ARD Online First, published on October 7, 2009 as 10.1136/ard.2009.108043 Ann Rheum Dis: first published as 10.1136/ard.2009.108043 on 7 October 2009. Downloaded from Novel expression signatures identified by transcriptional analysis of separated leukocyte subsets in SLE and vasculitis 1Paul A Lyons, 1Eoin F McKinney, 1Tim F Rayner, 1Alexander Hatton, 1Hayley B Woffendin, 1Maria Koukoulaki, 2Thomas C Freeman, 1David RW Jayne, 1Afzal N Chaudhry, and 1Kenneth GC Smith. 1Cambridge Institute for Medical Research and Department of Medicine, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0XY, UK 2Roslin Institute, University of Edinburgh, Roslin, Midlothian, EH25 9PS, UK Correspondence should be addressed to Dr Paul Lyons or Prof Kenneth Smith, Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0XY, UK. Telephone: +44 1223 762642, Fax: +44 1223 762640, E-mail: [email protected] or [email protected] Key words: Gene expression, autoimmune disease, SLE, vasculitis Word count: 2,906 The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non-exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article (if accepted) to be published in Annals of the Rheumatic Diseases and any other BMJPGL products to exploit all subsidiary rights, as set out in their licence (http://ard.bmj.com/ifora/licence.pdf). http://ard.bmj.com/ on September 29, 2021 by guest. Protected copyright. 1 Copyright Article author (or their employer) 2009.
    [Show full text]
  • (CONDCA) Disease Caused by AGTPBP1 Gene Mutations: the Purkinje Cell Degeneration Mouse As an Animal Model for the Study of This Human Disease
    biomedicines Review The Childhood-Onset Neurodegeneration with Cerebellar Atrophy (CONDCA) Disease Caused by AGTPBP1 Gene Mutations: The Purkinje Cell Degeneration Mouse as an Animal Model for the Study of this Human Disease Fernando C. Baltanás 1,* , María T. Berciano 2, Eugenio Santos 1 and Miguel Lafarga 3 1 Lab.1, CIC-IBMCC, University of Salamanca-CSIC and CIBERONC, 37007 Salamanca, Spain; [email protected] 2 Department of Molecular Biology and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), University of Cantabria-IDIVAL, 39011 Santander, Spain; [email protected] 3 Department of Anatomy and Cell Biology and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), University of Cantabria-IDIVAL, 39011 Santander, Spain; [email protected] * Correspondence: [email protected]; Tel.: +34-923294801 Abstract: Recent reports have identified rare, biallelic damaging variants of the AGTPBP1 gene that cause a novel and documented human disease known as childhood-onset neurodegeneration with cerebellar atrophy (CONDCA), linking loss of function of the AGTPBP1 protein to human neurode- Citation: Baltanás, F.C.; Berciano, generative diseases. CONDCA patients exhibit progressive cognitive decline, ataxia, hypotonia or M.T.; Santos, E.; Lafarga, M. The muscle weakness among other clinical features that may be fatal. Loss of AGTPBP1 in humans Childhood-Onset Neurodegeneration recapitulates the neurodegenerative course reported in a well-characterised murine animal model with Cerebellar Atrophy (CONDCA) harbouring loss-of-function mutations in the AGTPBP1 gene. In particular, in the Purkinje cell degen- AGTPBP1 Disease Caused by Gene eration (pcd) mouse model, mutations in AGTPBP1 lead to early cerebellar ataxia, which correlates Mutations: The Purkinje Cell with the massive loss of cerebellar Purkinje cells.
    [Show full text]
  • Overdispersed Gene Expression Characterizes Schizophrenic Brains
    bioRxiv preprint doi: https://doi.org/10.1101/441527; this version posted October 13, 2018. 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 4.0 International license. Overdispersed gene expression characterizes schizophrenic brains Guangzao Huang1,2§, Daniel Osorio3§, Jinting Guan1,2, Guoli Ji1,2,4,* and James J. Cai3,5,6,* 1Department of Automation, Xiamen University, Xiamen 361005, China 2Xiamen Research Institute of National Center of Healthcare Big Data, Xiamen 361005, China 3Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA 4Innovation Center for Cell Signaling Network, Xiamen University, Xiamen 361005, China 5Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843, USA 6Interdisciplinary Program of Genetics, Texas A&M University, College Station, TX 77843, USA §These authors contributed equally to this paper *Corresponding authors: Guoli Ji -- Department of Automation, Xiamen University, Xiamen 361005, China. James J. Cai -- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA. Telephone: 1-979-458-5482, FAX: 1-979-847-8981, email address: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/441527; this version posted October 13, 2018. 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 4.0 International license.
    [Show full text]
  • Tubulin Polyglutamylation Is a General Traffic-Control Mechanism In
    © 2020. Published by The Company of Biologists Ltd | Journal of Cell Science (2020) 133, jcs241802. doi:10.1242/jcs.241802 RESEARCH ARTICLE Tubulin polyglutamylation is a general traffic-control mechanism in hippocampal neurons Satish Bodakuntla1,2, Anne Schnitzler3, Cristopher Villablanca4,5, Christian Gonzalez-Billault4,5, Ivan Bieche3,6, Carsten Janke1,2,* and Maria M. Magiera1,2,* ABSTRACT Banker, 2016), relies to a large extent on the microtubule Neurons are highly complex cells that heavily rely on intracellular cytoskeleton (Conde and Cáceres, 2009). In differentiated transport to distribute a range of functionally essential cargoes within neurons, one of the key functions of microtubules is intracellular the cell. Post-translational modifications of tubulin are emerging transport (Nirschl et al., 2017), which ensures the delivery of a large as mechanisms for regulating microtubule functions, but their impact variety of functionally different cargoes, such as organelles on neuronal transport is only marginally understood. Here, we have (mitochondria, lysosomes and endosomes), proteins or mRNAs to systematically studied the impact of post-translational polyglutamylation specific target sites inside axons or dendrites (Maday et al., 2014). on axonal transport. In cultured hippocampal neurons, deletion of a A key question is thus how transport of those different cargoes is single deglutamylase, CCP1 (also known as AGTPBP1), is sufficient temporally and spatially controlled in order to meet the ever- to induce abnormal accumulation of polyglutamylation, i.e. changing requirements of different neuronal compartments, e.g. hyperglutamylation. We next investigated how hyperglutamylation synapses, which need to be replenished in receptors for their activity affects axonal transport of a range of functionally different neuronal (Choquet and Triller, 2013).
    [Show full text]
  • Brain-Region-Specific Contributions of Foxp1 to Autism And
    BRAIN-REGION-SPECIFIC CONTRIBUTIONS OF FOXP1 TO AUTISM AND INTELLECTUAL DISABILITY PHENOTYPES Daniel John Araujo APPROVED BY SUPERVISORY COMMITTEE: Amelia J. Eisch, Ph.D. (Chair) _____________________________ Genevieve Konopka, Ph.D. (Mentor) _____________________________ Craig M. Powell, M.D., Ph.D. _____________________________ Lenora J. Volk, Ph.D. _____________________________ Jiang Wu, Ph.D. _____________________________ DEDICATION I would like to thank my thesis advisor Dr. Genevieve Konopka who has always pushed me to strive for excellence in my work. It’s been an honor to study neuroscience under her supervision and she will serve as an example for the rest of my scientific career. I would like to thank my wife Sarah Teresita Vega for her unwavering love and patience. Sarah has been my best friend for the past nine years and her encouragement has allowed me to face any challenge with grit. I also thank my thesis committee members for all of their suggestions on how to improve my research. I would like to thank Dr. Timothy Raabe and Dr. Nancy Street for their continuous support of both my undergraduate and graduate career. Finally, I dedicate this dissertation to my grandparents George Cuellar Araujo and Margarita Salinas Araujo who raised my two siblings and me. Any success I’ve had in life belongs to them. ii BRAIN-REGION-SPECIFIC CONTRIBUTIONS OF FOXP1 TO AUTISM AND INTELLECTUAL DISABILITY PHENOTYPES By DANIEL JOHN ARAUJO, B.S. DISSERTATION Presented to the Faculty of the Graduate School of Biomedical Sciences at The University of Texas Southwestern Medical Center In Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY The University of Texas Southwestern Medical Center Dallas, Texas August 11, 2017 iii Copyright By Daniel John Araujo, 2017 All Rights Reserved iv BRAIN-REGION-SPECIFIC CONTRIBUTIONS OF FOXP1 TO AUTISM AND INTELLECTUAL DISABILITY PHENOTPES Publication No.
    [Show full text]