ArticleThe Journal of biological chemistry2017
GluA1 subunit ubiquitination mediates amyloid-β-induced loss of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 67 citations in OpenAlex.
- UPS-mediated P-glycoprotein regulation in Alzheimer's disease: pharmacological implications for the amyloid pathology.Molecular biology reports · 2026Review
- Posttranslational modifications of AMPA receptors in synaptic function and memory.Cellular and molecular life sciences : CMLS · 2026Review
- The interaction between neurotransmitter receptor activity and amyloid-β pathology in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Review
- Role of Ion Channels in Alzheimer's Disease Pathophysiology.The Journal of membrane biology · 2025Review
- Amyloid-β-Driven Synaptic Deficits Are Mediated by Synaptic Removal of GluA3-Containing AMPA Receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- AMPA receptor diffusional trapping machinery as an early therapeutic target in neurodegenerative and neuropsychiatric disorders.Translational neurodegeneration · 2025Review
- Lysine 473 Regulates the Progression of SLC7A11, the Cystine/Glutamate Exchanger, through the Secretory Pathway.International journal of molecular sciences · 2024Article
- The Role of RIN3 Gene in Alzheimer's Disease Pathogenesis: a Comprehensive Review.Molecular neurobiology · 2024Review
- Pathogenesis of Depression in Alzheimer's Disease.Neurochemical research · 2024Review
- Glua1 Ubiquitination in Synaptic Plasticity and Cognitive Functions: Implications for Neurodegeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Clathrin mediated endocytosis in Alzheimer's disease: cell type specific involvement in amyloid beta pathology.Frontiers in aging neuroscience · 2024Review
- GluN2A or GluN2B subunits of the NMDA receptor contribute to changes in neuronal excitability and impairments in LTP in the hippocampus of aging mice but do not mediate detrimental effects of oligomeric Aβ (1-42).Frontiers in aging neuroscience · 2024Article
- Fluorescence lifetime imaging of AMPA receptor endocytosis in living neurons: effects of Aβ and PP1.Frontiers in molecular neuroscience · 2024Article
- A clathrin mediated endocytosis scaffolding protein, Intersectin 1, changes in an isoform, brain region, and sex specific manner in Alzheimer's disease.Frontiers in neuroscience · 2024Article
- Molecular Mechanisms of AMPA Receptor Trafficking in the Nervous System.International journal of molecular sciences · 2023Review
- Alzheimer's Disease beyond Calcium Dysregulation: The Complex Interplay between Calmodulin, Calmodulin-Binding Proteins and Amyloid Beta from Disease Onset through Progression.Current issues in molecular biology · 2023Review
- Ubiquitination of the GluA1 Subunit of AMPA Receptors Is Required for Synaptic Plasticity, Memory, and Cognitive Flexibility.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Aß Pathology and Neuron-Glia Interactions: A Synaptocentric View.Neurochemical research · 2023Review
- A novel bio-inspired strategy to prevent amyloidogenesis and synaptic damage in Alzheimer's disease.Molecular psychiatry · 2022Article
- The Role of AMPARs Composition and Trafficking in Synaptic Plasticity and Diseases.Cellular and molecular neurobiology · 2022Review
Corrections and comments
- Commented on by
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The accumulation of soluble amyloid-β (Aβ) peptides produces profound neuronal changes in the brain during the pathogenesis of Alzheimer's disease. Excessive levels of Aβ disrupt excitatory synaptic transmission by promoting the removal of synaptic AMPA receptors (AMPARs), dendritic spine loss, and synaptic depression. Recently, activity-dependent ubiquitination of the GluA1 subunit has been shown to regulate the intracellular sorting of AMPARs toward late endosomes for degradation. However, whether this ubiquitin signaling pathway mediates Aβ-induced loss of surface AMPARs is unknown. In this study, we demonstrate that acute exposure of cultured neurons to soluble Aβ oligomers induces AMPAR ubiquitination concomitant with the removal of AMPARs from the plasma membrane. Importantly, expression of the GluA1 ubiquitin-deficient mutants inhibited the adverse effects of Aβ on the surface expression of AMPARs in neurons. Furthermore, we revealed the cross-talk between GluA1 ubiquitination and phosphorylation, in particular phosphorylation at Ser-845, which is crucial for AMPAR recycling and is known to be dephosphorylated in the presence of Aβ. Our data showed that the GluA1 ubiquitin-deficient mutant enhances GluA1 phosphorylation on Ser-845. Conversely, the GluA1 S845D phosphomimetic mutant reduced binding with Nedd4-1 and hence the ubiquitination of AMPARs. Importantly, the GluA1 S845D mutant also prevented Aβ-induced removal of surface AMPARs. Taken together, these findings provide the first demonstration of the dynamic cross-modulation of GluA1 ubiquitination and phosphorylation, a process that is perturbed by Aβ, in regulating the membrane sorting decision that ultimately determines the number of AMPARs on the cell surface.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.