Complex alteration of NMDA receptors in transgenic Huntington's disease mouse brain: analysis of mRNA and protein expression, plasma membrane association, interacting proteins, and phosphorylation

2003 ◽  
Vol 14 (3) ◽  
pp. 624-636 ◽  
Author(s):  
Ruth Luthi-Carter ◽  
Barbara L Apostol ◽  
Anthone W Dunah ◽  
Molly M DeJohn ◽  
Laurie A Farrell ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Protein Expression ◽  
Nmda Receptors ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mouse Brain ◽  
Membrane Association ◽  
Interacting Proteins ◽  
Mrna And Protein Expression

scholarly journals Identification of Full-Length Wild-Type and Mutant Huntingtin Interacting Proteins by Crosslinking Immunoprecipitation in Mice Brain Cortex

2021 ◽  
pp. 1-13
Author(s):  
Karen A. Sap ◽  
Arzu Tugce Guler ◽  
Aleksandra Bury ◽  
Dick Dekkers ◽  
Jeroen A.A. Demmers ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Brain Cortex ◽  
Full Length ◽  
Biological Processes ◽  
Interacting Proteins ◽  
Mutant Huntingtin ◽  
Wild Type ◽  
Mutant Huntingtin Protein ◽  
Mice Brain

Background: Huntington’s disease is a neurodegenerative disorder caused by a CAG expansion in the huntingtin gene, resulting in a polyglutamine expansion in the ubiquitously expressed mutant huntingtin protein. Objective: Here we set out to identify proteins interacting with the full-length wild-type and mutant huntingtin protein in the mice cortex brain region to understand affected biological processes in Huntington’s disease pathology. Methods: Full-length huntingtin with 20 and 140 polyQ repeats were formaldehyde-crosslinked and isolated via their N-terminal Flag-tag from 2-month-old mice brain cortex. Interacting proteins were identified and quantified by label-free liquid chromatography-mass spectrometry (LC-MS/MS). Results: We identified 30 interactors specific for wild-type huntingtin, 14 interactors specific for mutant huntingtin and 14 shared interactors that interacted with both wild-type and mutant huntingtin, including known interactors such as F8a1/Hap40. Syt1, Ykt6, and Snap47, involved in vesicle transport and exocytosis, were among the proteins that interacted specifically with wild-type huntingtin. Various other proteins involved in energy metabolism and mitochondria were also found to associate predominantly with wild-type huntingtin, whereas mutant huntingtin interacted with proteins involved in translation including Mapk3, Eif3h and Eef1a2. Conclusion: Here we identified both shared and specific interactors of wild-type and mutant huntingtin, which are involved in different biological processes including exocytosis, vesicle transport, translation and metabolism. These findings contribute to the understanding of the roles that wild-type and mutant huntingtin play in a variety of cellular processes both in healthy conditions and Huntington’s disease pathology.

scholarly journals Cystamine increases l-cysteine levels in Huntington's disease transgenic mouse brain and in a PC12 model of polyglutamine aggregation

2004 ◽  
Vol 91 (2) ◽  
pp. 413-422 ◽  
Author(s):  
Jonathan H. Fox ◽  
David S. Barber ◽  
Bhupinder Singh ◽  
Birgit Zucker ◽  
Mary K. Swindell ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Transgenic Mouse ◽  
Mouse Brain ◽  
Polyglutamine Aggregation

scholarly journals Imbalance of p75NTR/TrkB protein expression in Huntington’s disease: implication for neuroprotective therapies

2013 ◽  
Vol 4 (4) ◽  
pp. e595-e595 ◽  
Author(s):  
V Brito ◽  
M Puigdellívol ◽  
A Giralt ◽  
D del Toro ◽  
J Alberch ◽  
...  
Keyword(s):  
Protein Expression ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neuroprotective Therapies

Distribution of SV2C mRNA and protein expression in the mouse brain with a particular emphasis on the basal ganglia system

2011 ◽  
Vol 1367 ◽  
pp. 130-145 ◽  
Author(s):  
D. Dardou ◽  
D. Dassesse ◽  
L. Cuvelier ◽  
T. Deprez ◽  
M. De Ryck ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Protein Expression ◽  
Mouse Brain ◽  
Mrna And Protein Expression

Hypothesis: huntingtin may function in membrane association and vesicular traffickingThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB — Membrane Proteins in Health and Disease.

2006 ◽  
Vol 84 (6) ◽  
pp. 912-917 ◽  
Author(s):  
Ray Truant ◽  
Randy Atwal ◽  
Anjee Burtnik
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Protein Interactions ◽  
Cell Biology ◽  
Genetic Disorder ◽  
Scaffolding Protein ◽  
Membrane Association ◽  
Protein Protein Interactions ◽  
Polyglutamine Expansion ◽  
Exact Function

Huntington’s disease is a progressive neurodegenerative genetic disorder that is caused by a CAG triplet-repeat expansion in the first exon of the IT15 gene. This CAG expansion results in polyglutamine expansion in the 350 kDa huntingtin protein. The exact function of huntingtin is unknown. Understanding the pathological triggers of mutant huntingtin, and distinguishing the cause of disease from downstream effects, is critical to designing therapeutic strategies and defining long- and short-term goals of therapy. Many studies that have sought to determine the functions of huntingtin by determining huntingtin’s protein–protein interactions have been published. Through these studies, huntingtin has been seen to interact with a large number of proteins, and is likely a scaffolding protein for protein–protein interactions. Recently, using imaging, integrative proteomics, and cell biology, huntingtin has been defined as a membrane-associated protein, with activities related to axonal trafficking of vesicles and mitochondria. These functions have also been attributed to some huntingtin-interacting proteins. Additionally, discoveries of a membrane association domain and a palmitoylation site in huntingtin reinforce the fact that huntingtin is membrane associated. In Huntington’s disease mouse and fly models, axonal vesicle trafficking is inhibited, and lack of proper uptake of neurotrophic factors may be an important pathological trigger leading to striatal cell death in Huntington’s disease. Here we discuss recent advances from many independent groups and methodologies that are starting to resolve the elusive function of huntingtin in vesicle transport, and evidence that suggests that huntingtin may be directly involved in membrane interactions.

scholarly journals Huntington’s disease and NMDA receptors; a new arena for therapeutic development

2018 ◽  
Vol 2 (1) ◽  
pp. 1-13
Author(s):  
Mohamed Megahed ◽  
Mona El-Azab ◽  
Moushira El Sayed ◽  
Yasser Moustafa
Keyword(s):  
Nmda Receptors ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Therapeutic Development

scholarly journals Altered Hypothalamic Protein Expression in a Rat Model of Huntington's Disease

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e47240 ◽  
Author(s):  
Wei-na Cong ◽  
Huan Cai ◽  
Rui Wang ◽  
Caitlin M. Daimon ◽  
Stuart Maudsley ◽  
...  
Keyword(s):  
Protein Expression ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rat Model

scholarly journals Patterns of mRNA and protein expression for 12 GABAA receptor subunits in the mouse brain

Neuroscience ◽  
2013 ◽  
Vol 236 ◽  
pp. 345-372 ◽  
Author(s):  
H. Hörtnagl ◽  
R.O. Tasan ◽  
A. Wieselthaler ◽  
E. Kirchmair ◽  
W. Sieghart ◽  
...  
Keyword(s):  
Protein Expression ◽  
Gabaa Receptor ◽  
Mouse Brain ◽  
Mrna And Protein Expression ◽  
Gabaa Receptor Subunits

Anatomical characterization of cytoglobin and neuroglobin mRNA and protein expression in the mouse brain

2010 ◽  
Vol 1331 ◽  
pp. 58-73 ◽  
Author(s):  
Christian Ansgar Hundahl ◽  
Gregg C. Allen ◽  
Jens Hannibal ◽  
Katrine Kjaer ◽  
Jens F. Rehfeld ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mouse Brain ◽  
Mrna And Protein Expression ◽  
Anatomical Characterization

scholarly journals Location, Location, Location: Contrasting Roles of Synaptic and Extrasynaptic NMDA Receptors in Huntington's Disease

Neuron ◽  
2010 ◽  
Vol 65 (2) ◽  
pp. 145-147 ◽  
Author(s):  
Michael S. Levine ◽  
Carlos Cepeda ◽  
Véronique M. André
Keyword(s):  
Nmda Receptors ◽  
Huntington's Disease ◽  
Huntington’S Disease
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