ArticleThe Journal of biological chemistry2011
Impaired alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking and function by mutant huntingtin.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 59 citations in OpenAlex.
- 3-Nitropropionic Acid-Induced Huntington's Disease in Preclinical Models: Mechanisms, Peripheral Toxicities, Model Gaps, and Future Directions.Molecular neurobiology · 2026Review
- Huntingtin and its allies at the cortico-striatal synapse.Cell death & disease · 2026Review
- Research advances in huntingtin-associated protein 1 and its application prospects in diseases.Frontiers in neuroscience · 2024Review
- Molecular Mechanisms of AMPA Receptor Trafficking in the Nervous System.International journal of molecular sciences · 2023Review
- Mutant-Huntingtin Molecular Pathways Elucidate New Targets for Drug Repurposing.International journal of molecular sciences · 2023Review
- Regulation of different phases of AMPA receptor intracellular transport by 4.1N and SAP97.eLife · 2023Article
- Huntingtin-associated protein 1-associated intracellular trafficking in neurodegenerative diseases.Frontiers in aging neuroscience · 2023Review
- Pathogenesis of Huntington's Disease: An Emphasis on Molecular Pathways and Prevention by Natural Remedies.Brain sciences · 2022Review
- Protein Kinase CK2 and Its Potential Role as a Therapeutic Target in Huntington's Disease.Biomedicines · 2022Review
- Synaptic Dysfunction in Huntington's Disease: Lessons from Genetic Animal Models.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2022Article
- Calcium dysregulation and compensation in cortical pyramidal neurons of the R6/2 mouse model of Huntington's disease.Journal of neurophysiology · 2021Article
- Calcium Permeable-AMPA Receptors and Excitotoxicity in Neurological Disorders.Frontiers in neural circuits · 2021Review
- Huntingtin and the Synapse.Frontiers in cellular neuroscience · 2021Review
- Autism spectrum disorder-like behavior caused by reduced excitatory synaptic transmission in pyramidal neurons of mouse prefrontal cortex.Nature communications · 2020Article
- Glucocorticoid-mediated ER-mitochondria contacts reduce AMPA receptor and mitochondria trafficking into cell terminus via microtubule destabilization.Cell death & disease · 2018Article
- Huntington's Disease: Mechanisms of Pathogenesis and Therapeutic Strategies.Cold Spring Harbor perspectives in medicine · 2017Review
- Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders.Neural plasticity · 2017Review
- Exosomes and Homeostatic Synaptic Plasticity Are Linked to Each other and to Huntington's, Parkinson's, and Other Neurodegenerative Diseases by Database-Enabled Analyses of Comprehensively Curated Datasets.Frontiers in neuroscience · 2017Article
- Huntingtin-associated protein 1: Eutherian adaptation from a TRAK-like protein, conserved gene promoter elements, and localization in the human intestine.BMC evolutionary biology · 2016Article
- DISC1 is a coordinator of intracellular trafficking to shape neuronal development and connectivity.The Journal of physiology · 2016Review
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Emerging evidence from studies of Huntington disease (HD) pathophysiology suggests that huntingtin (htt) and its associated protein HAP1 participate in intracellular trafficking and synaptic function. However, it is largely unknown whether AMPA receptor trafficking, which is crucial for controlling the efficacy of synaptic excitation, is affected by the mutant huntingtin with polyglutamine expansion (polyQ-htt). In this study, we found that expressing polyQ-htt in neuronal cultures significantly decreased the amplitude and frequency of AMPAR-mediated miniature excitatory postsynaptic current (mEPSC), while expressing wild-type huntingtin (WT-htt) increased mEPSC. AMPAR-mediated synaptic transmission was also impaired in a transgenic mouse model of HD expressing polyQ-htt. The effect of polyQ-htt on mEPSC was mimicked by knockdown of HAP1 and occluded by the dominant negative HAP1. Moreover, we found that huntingtin affected mESPC via a mechanism depending on the kinesin motor protein, KIF5, which controls the transport of GluR2-containing AMPARs along microtubules in dendrites. The GluR2/KIF5/HAP1 complex was disrupted and dissociated from microtubules in the HD mouse model. Together, these data suggest that AMPAR trafficking and function is impaired by mutant huntingtin, presumably due to the interference of KIF5-mediated microtubule-based transport of AMPA receptors. The diminished strength of glutamatergic transmission could contribute to the deficits in movement control and cognitive processes in HD conditions.
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