The Angelman syndrome protein Ube3a/E6AP is required for Golgi acidification and surface protein sialylation

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Kathryn H CondonMichael D Ehlers

Abstract

Angelman syndrome (AS) is a severe disorder of postnatal brain development caused by neuron-specific loss of the HECT (homologous to E6AP carboxy terminus) domain E3 ubiquitin ligase Ube3a/E6AP. The cellular role of Ube3a remains enigmatic despite recent descriptions of synaptic and behavioral deficits in AS mouse models. Although neuron-specific imprinting is thought to limit the disease to the brain, Ube3a is expressed ubiquitously, suggesting a broader role in cellular function. In the current study, we demonstrate a profound structural disruption and cisternal swelling of the Golgi apparatus (GA) in the cortex of AS (UBE3A(m-/p+)) mice. In Ube3a knockdown cell lines and UBE3A(m-/p+) cortical neurons, the GA is severely under-acidified, leading to osmotic swelling. Both in vitro and in vivo, the loss of Ube3a and corresponding elevated pH of the GA is associated with a marked reduction in protein sialylation, a process highly dependent on intralumenal Golgi pH. Altered ion homeostasis of the GA may provide a common cellular pathophysiology underlying the diverse plasticity and neurodevelopmental deficits associated with AS.

References

Dec 1, 1978·The Journal of Cell Biology·A TartakoffM Détraz
Feb 1, 1989·The Journal of Cell Biology·G GriffithsK Simons
Sep 1, 1983·The Journal of Cell Biology·F V Alonso-Caplen, R W Compans
Jan 18, 1994·Proceedings of the National Academy of Sciences of the United States of America·E Ioffe, P Stanley
Jun 28, 1996·The Journal of Biological Chemistry·O SeksekA S Verkman
Sep 1, 1997·Nature Genetics·C RougeulleMarc Lalande
Sep 4, 1997·Nature·J F PresleyJ Lippincott-Schwartz
Feb 18, 1998·Brain Research. Developmental Brain Research·C CastilloE Recio-Pinto
Jun 17, 1998·Proceedings of the National Academy of Sciences of the United States of America·Juan L LlopisR Y Tsien
Mar 13, 1999·The Journal of Biological Chemistry·J Farinas, A S Verkman
Jun 22, 1999·The Journal of Biological Chemistry·S KumarPeter M Howley
Jun 23, 1999·Proceedings of the National Academy of Sciences of the United States of America·K A SheikhRonald L Schnaar
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·H OdaPeter M Howley
Mar 17, 2000·Science·E Saxon, Carolyn R Bertozzi
Apr 5, 2000·The Journal of Biological Chemistry·F B Schapiro, Sergio Grinstein
May 2, 2000·The Journal of Biological Chemistry·C ChenK J Colley
Oct 14, 2000·Annual Review of Cell and Developmental Biology·J Lippincott-SchwartzK Hirschberg
Nov 3, 2001·Science·S SchochE T Kavalali
Mar 12, 2002·Glycobiology·Eric G Berger
Apr 10, 2002·American Journal of Physiology. Cell Physiology·Christopher L BrettRajini Rao
Apr 5, 2003·Annual Review of Biochemistry·John B Lowe, Jamey D Marth
May 22, 2003·Progress in Biophysics and Molecular Biology·Catherine van VlietPaul A Gleeson
Jul 2, 2003·European Journal of Medicinal Chemistry·B MasereelD Laeckmann
Jul 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·David J VocadloCarolyn R Bertozzi
Jan 7, 2004·Nature Reviews. Molecular Cell Biology·Juan S Bonifacino
Feb 21, 2004·Nature Reviews. Neuroscience·Ralf Kleene, Melitta Schachner
Jul 21, 2004·The Journal of Biological Chemistry·Eric M CooperPeter M Howley
Aug 12, 2004·Physiology·Paul ParoutisSergio Grinstein
May 10, 2005·Biochimica Et Biophysica Acta·Hemmo H Meyer
Jul 30, 2005·Molecular Endocrinology·Sung Yun JungJun Qin
Jan 24, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Simon HirotaLuke J Janssen
Feb 16, 2006·The Journal of General Physiology·Patrick J Stocker, Eric S Bennett
Mar 21, 2006·Journal of the Neurological Sciences·Nicholas K GonatasJacqueline O Gonatas
Sep 9, 2006·Cell·Kazuaki Ohtsubo, Jamey D Marth
Sep 9, 2006·Cell Motility and the Cytoskeleton·Francisco Lázaro-DiéguezGustavo Egea
Jan 11, 2007·The Biochemical Journal·Emily R SlepkovLarry Fliegel
Oct 26, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Dmytro IsaevGregory L Holmes
Dec 7, 2007·Nature Reviews. Neuroscience·Urs Rutishauser
Feb 27, 2008·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Li ZhengYang Ke
Apr 17, 2008·Nature Reviews. Genetics·Brett S Abrahams, Daniel H Geschwind
May 8, 2008·Bioscience, Biotechnology, and Biochemistry·Shou Takashima
Jun 25, 2008·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Inga HartingNicole I Wolf
Jul 9, 2008·Trends in Molecular Medicine·Ajit Varki
Jul 16, 2008·Science·Eric M MorrowChristopher A Walsh
Sep 5, 2008·Current Protocols in Microbiology·Robert C Burghardt, Robert Droleskey
Sep 17, 2008·Nature Cell Biology·Yusuke MaedaTaroh Kinoshita
Oct 11, 2008·Journal of Lipid Research·Robert K YuMakoto Yanagisawa
Jan 22, 2009·Journal of Neuroscience Research·Ronald L Schnaar, Pablo H H Lopez
Mar 12, 2009·Journal of Cellular Physiology·Antti RivinojaSakari Kellokumpu
Mar 27, 2009·Human Molecular Genetics·Vishwanathan HucthagowderZsolt Urban
May 1, 2009·Nature·Joseph T GlessnerHakon Hakonarson
May 12, 2009·Nature Neuroscience·Koji YashiroBenjamin D Philpot
Jul 22, 2009·Experimental Cell Research·Ingrid RoxrudHarald Stenmark
Aug 4, 2009·American Journal of Human Genetics·Dianne F NewburyAnthony P Monaco
Sep 2, 2009·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Manuel Castro-GagoVanessa María Rodríguez-Mugico
Oct 17, 2009·Chemical Reviews·Junyan Han, Kevin Burgess
Dec 10, 2009·Nature Reviews. Molecular Cell Biology·Joseph R CaseyJohn Orlowski
Jan 27, 2010·FEBS Letters·John C Edwards, Christina R Kahl
Mar 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Masaaki Sato, Michael P Stryker
May 7, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Elena RepnikovaVladislav M Panin
Jul 30, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Stormy J Chamberlain, Marc Lalande
Oct 16, 2010·American Journal of Medical Genetics. Part a·Richard J SchroerCharles E Schwartz
Oct 29, 2010·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Charles A Williams
Dec 1, 2010·The Journal of Biological Chemistry·Tara A SchwetzEric S Bennett
Dec 3, 2010·Developmental Medicine and Child Neurology·Sarika U PetersElisabeth A Wilde
Jan 18, 2011·The Journal of Biological Chemistry·Chunjuan Huang, Amy Chang
May 20, 2011·Trends in Neurosciences·Angela M MabbBenjamin D Philpot
Jul 19, 2011·Molecular and Cellular Neurosciences·Zofia M Lasiecka, Bettina Winckler
Dec 23, 2011·Nature·Hsien-Sung HuangBenjamin D Philpot
Feb 23, 2012·Proceedings of the National Academy of Sciences of the United States of America·Fredrik SwiftWilliam E Louch
May 31, 2012·Molecular and Cellular Biology·Gustavo Martínez-NoëlPeter M Howley
Jan 4, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sheng MiaoZhi-Qi Xiong

Citations

Sep 13, 2013·International Journal of Molecular Sciences·Mariana G Bexiga, Jeremy C Simpson
Oct 5, 2013·Molecular Neurobiology·Jimmy El Hokayem, Zafar Nawaz
May 17, 2015·FEBS Letters·Mateusz Cyryl Ambrozkiewicz, Hiroshi Kawabe
Dec 30, 2014·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Gunjan Joshi, Yanzhuang Wang
Nov 21, 2013·The Journal of Comparative Neurology·Matthew C JudsonBenjamin D Philpot
Mar 25, 2016·Current Opinion in Neurobiology·Cyril Hanus, Michael D Ehlers
May 15, 2015·Journal of Inherited Metabolic Disease·Sven PotelleFrançois Foulquier
May 30, 2015·Pediatric Clinics of North America·Louisa Kalsner, Stormy J Chamberlain
Jun 25, 2016·The Journal of Comparative Neurology·Alain C BuretteRichard J Weinberg
May 10, 2017·The Journal of Biological Chemistry·Karina OberheideThomas J Jentsch
Feb 7, 2014·Journal of Neurophysiology·Jada J Hallengren, Ryan J Vaden
Oct 27, 2018·Molecular Autism·Alain C BuretteRichard J Weinberg
May 4, 2017·Proceedings of the National Academy of Sciences of the United States of America·Masashi Tachikawa, Atsushi Mochizuki
Sep 6, 2017·Frontiers in Cell and Developmental Biology·Li MaEric M Morrow
Nov 22, 2013·Biochemical Society Transactions·Michael D Ehlers

Related Concepts

Venus protein, Bacteria
Transfectam
Ube3a protein, mouse
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Insula of Reil
Embryonic Structures, Mammalian
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Golgi Apparatus
Hydrogen-Ion Concentration
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