Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form nuclear and cytoplasmic aggregates in cell culture

Human Molecular Genetics
J K CooperC A Ross

Abstract

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by an expanding CAG repeat coding for polyglutamine in the huntingtin protein. Recent data have suggested the possibility that an N-terminal fragment of huntingtin may aggregate in neurons of patients with HD, both in the cytoplasm, forming dystrophic neurites, and in the nucleus, forming intranuclear neuronal inclusion bodies. An animal model of HD using the short N-terminal fragment of huntingtin has also been found to have intranuclear inclusions and this same fragment can aggregate in vitro . We have now developed a cell culture model demonstrating that N-terminal fragments of huntingtin with expanded glutamine repeats aggregate both in the cytoplasm and in the nucleus. Neuroblastoma cells transiently transfected with full-length huntingtin constructs with either a normal or expanded repeat had diffuse cytoplasmic localization of the protein. In contrast, cells transfected with truncated N-terminal fragments showed aggregation only if the glutamine repeat was expanded. The aggregates were often ubiquitinated. The shorter truncated product appeared to form more aggregates in the nucleus. Cells transfected with the expanded repeat construct but not t...Continue Reading

Citations

Dec 10, 1999·Annals of Neurology·S KuemmerleR J Ferrante
Mar 26, 1999·Movement Disorders : Official Journal of the Movement Disorder Society·H D RosasM E Cudkowicz
Apr 5, 2001·Journal of Neuroscience Research·A W Deckel
Aug 31, 2000·Molecular Neurobiology·X J Li
Jun 25, 2013·Molecules and Cells·Tiffany W Todd, Janghoo Lim
Jul 18, 2012·Apoptosis : an International Journal on Programmed Cell Death·Xin-An LiuJian-Zhi Wang
Apr 4, 2008·Cellular and Molecular Neurobiology·Sadaf KasraieMostafa Moin
Mar 22, 2013·Molecular Neurobiology·Santosh JadhavMichal Novak
Mar 1, 2009·Interdisciplinary Sciences, Computational Life Sciences·Miki NakanoShigenori Tanaka
Mar 31, 2007·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Holly B Kordasiewicz, Christopher M Gomez
May 12, 2001·Mechanisms of Ageing and Development·D A Butterfield, J Kanski
Aug 15, 2000·Trends in Neurosciences·J H Cha
Feb 22, 2001·Trends in Neurosciences·E CattaneoS Sipione
Jun 4, 1999·Trends in Neurosciences·P H ReddyD A Tagle
Nov 20, 1998·Trends in Genetics : TIG·A Kakizuka
Mar 27, 2003·Progress in Neuro-psychopharmacology & Biological Psychiatry·Miriam A Hickey, Marie Françoise Chesselet
Nov 24, 1999·Neuroscience Letters·M F Peters, C A Ross
Apr 4, 2003·The International Journal of Biochemistry & Cell Biology·Geoffrey M Goellner, Martin Rechsteiner
Mar 25, 2000·Clinical Genetics·C L Wellington, M R Hayden
Jul 20, 2010·Nature Cell Biology·Brinda RavikumarDavid C Rubinsztein
Mar 4, 2000·The Biochemical Journal·R A FurlongD C Rubinsztein
Apr 12, 2001·Neuropathology and Applied Neurobiology·K A Sieradzan, D M Mann
Jan 5, 2000·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·S YasudaA Kakizuka
Aug 10, 2002·The European Journal of Neuroscience·Ester Martín-AparicioJosé J Lucas
Feb 12, 2011·The Journal of Biological Chemistry·Tamara RatovitskiChristopher A Ross
Feb 11, 2009·The Journal of Biological Chemistry·Tamara RatovitskiChristopher A Ross
Oct 13, 2006·Antioxidants & Redox Signaling·Mark P Mattson
Oct 18, 2005·Hybridoma·Shu-Yan CongJosephine C Dorsman
Apr 10, 1999·Human Molecular Genetics·K SathasivamG P Bates
Nov 26, 2010·Human Molecular Genetics·Mohamed R MughalMark P Mattson
Feb 11, 2011·Human Molecular Genetics·Andrew T N TebbenkampDavid R Borchelt
Sep 13, 2011·Nucleic Acids Research·Wlodzimierz J KrzyzosiakPiotr Kozlowski
Aug 6, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·N AroninM DiFiglia
Aug 6, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·C A RossD R Borchelt
Aug 6, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·A LunkesJ L Mandel
Aug 6, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·A S HackamM R Hayden
Oct 21, 1999·Journal of Medical Genetics·Y NarainD C Rubinsztein
Jul 7, 2012·PloS One·Yang-Nim ParkLois E Greene

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