Aggregation of N-terminal huntingtin is dependent on the length of its glutamine repeats

Human Molecular Genetics
S H Li, X J Li

Abstract

Huntington's disease (HD) is caused by expansion of a glutamine repeat in huntingtin. Mutant huntingtin contains 36-55 repeats in adult HD patients and >60 repeats in juvenile HD patients. An N-terminal fragment of mutant huntingtin forms aggregates in neuronal nuclei in the brains of transgenic mice and HD patients. Aggregation of expanded polyglutamine is thought to be a common pathological mechanism in HD and other glutamine repeat diseases. It is not clear how the length of the repeats is correlated with formation of protein aggregates. By expressing a series of huntingtin constructs encoding various glutamine repeats (23-150 units) in cultured cells we observed N-terminal fragments of huntingtin (amino acids 1-67 and 1-212), but not full-length huntingtins, with glutamine repeats >/=66 units formed protein aggregates. Huntingtin aggregation was not induced when the repeat was </=49 units and was markedly promoted by very long repeats >/=120 units. This study suggests that various N-terminal fragments of mutant huntingtin can form aggregates and that aggregation is prompted by lengthening the glutamine repeat.

Citations

Aug 31, 2000·Molecular Neurobiology·X J Li
Apr 11, 2013·Seminars in Immunopathology·Sang Won Park, Umut Ozcan
Feb 9, 2008·Histochemistry and Cell Biology·Karl BacosNils Wierup
Jun 25, 2013·Molecules and Cells·Tiffany W Todd, Janghoo Lim
Aug 15, 2000·Trends in Neurosciences·J H Cha
Jun 4, 1999·Trends in Neurosciences·P H ReddyD A Tagle
Nov 20, 1998·Trends in Genetics : TIG·A Kakizuka
Jan 18, 2003·Brain Research. Molecular Brain Research·Willeke M C van Roon-MomRussell G Snell
Oct 19, 2000·Neuroscience·D P McGowanR G Snell
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
Jan 16, 2013·The Journal of Biological Chemistry·Zhiqiang ZhengMarc I Diamond
Apr 11, 2008·The Journal of Biological Chemistry·Adam L OrrXiao-Jiang Li
Apr 10, 1999·Human Molecular Genetics·K SathasivamG P Bates
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·E PreisingerD Housman
Aug 6, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·A S HackamM R Hayden
Mar 14, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Adam L OrrXiao-Jiang Li
Dec 6, 2000·Proceedings of the National Academy of Sciences of the United States of America·T B FreemanO Isacson
Nov 6, 1998·Brain Pathology·G P BatesS W Davies
Jan 6, 1999·Proceedings of the National Academy of Sciences of the United States of America·P W FaberA C Hart
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·A KazantsevD Housman
Jul 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·Hideyuki MukaiRon R Kopito
Jan 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Ali KhoshnanPaul H Patterson
Aug 18, 2012·Journal of Biophysics·María Elena Chánez-Cárdenas, Edgar Vázquez-Contreras
Jul 4, 2012·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Xiao-Jiang Li, Shihua Li
Oct 23, 2015·Brain : a Journal of Neurology·Laura E ClemensHuu P Nguyen
May 23, 2009·Experimental Neurology·Jenny SassoneAndrea Ciammola
May 14, 2004·Journal of Neurochemistry·Michael D KaytorStephen T Warren
Mar 13, 2014·The Journal of Comparative Neurology·Dasa DolezalovaMartin Marsala
Sep 16, 2006·Molecular Aspects of Medicine·Brinda Ravikumar, David C Rubinsztein
Jul 26, 2005·Biochemical and Biophysical Research Communications·Hui-Fang TsaiMingli Hsieh
Apr 5, 2016·American Journal of Human Genetics·Adriana P RebeloStephan Zuchner
Jul 2, 2015·Human Molecular Genetics·Ching-Chieh ChouWilfried Rossoll
May 1, 1999·Experimental Neurology·A PetersénP Brundin

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.