ArticlePLoS biology2019
The deubiquitinase USP6 affects memory and synaptic plasticity through modulating NMDA receptor stability.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 43 citations in OpenAlex.
- Glycine Alleviates HMolecular neurobiology · 2026Article
- USP19 restores mitochondrial function in neurons by deubiquitinating FUS to alleviate trigeminal neuralgia.Experimental brain research · 2025Article
- Ubiquitination in the Nervous System: From Molecular Mechanisms to Disease Implications.Molecular neurobiology · 2025Review
- USP47 Regulates Excitatory Synaptic Plasticity and Modulates Seizures in Murine Models by Blocking Ubiquitinated AMPAR Degradation.Neuroscience bulletin · 2025Article
- Physiological roles and therapeutic implications of USP6.Cell death discovery · 2025Review
- Regulation of Synaptic NMDA Receptor Activity by Post-Translational Modifications.Neurochemical research · 2025Review
- ZBTB21 suppresses CRE-mediated transcription to impair synaptic function in Down syndrome.Science advances · 2024Article
- Metabolic reprogramming in astrocytes results in neuronal dysfunction in intellectual disability.Molecular psychiatry · 2024Article
- RNF220 is an E3 ubiquitin ligase for AMPA receptors to regulate synaptic transmission.Science advances · 2022Article
- A novel rat model for cerebral venous sinus thrombosis: verification of similarity to human disease via clinical analysis and experimental validation.Journal of translational medicine · 2022Article
- Deubiquitinases in Neurodegeneration.Cells · 2022Review
- Protein clearance strategies for disease intervention.Journal of neural transmission (Vienna, Austria : 1996) · 2022Review
- Historical perspective and progress on protein ubiquitination at glutamatergic synapses.Neuropharmacology · 2021Review
- Deficiency of the CYLD Impairs Fear Memory of Mice and Disrupts Neuronal Activity and Synaptic Transmission in the Basolateral Amygdala.Frontiers in cellular neuroscience · 2021Article
- Reduced Expression of Hippocampal GluN2A-NMDAR Increases Seizure Susceptibility and Causes Deficits in Contextual Memory.Frontiers in neuroscience · 2021Article
- Trisomy 21-induced dysregulation of microglial homeostasis in Alzheimer's brains is mediated by USP25.Science advances · 2021Article
- RAB39B Deficiency Impairs Learning and Memory Partially Through Compromising Autophagy.Frontiers in cell and developmental biology · 2020Article
- Overexpression of HumanFrontiers in cell and developmental biology · 2020Article
- Review
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Authors and funding
31 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ubiquitin-specific protease (USP) 6 is a hominoid deubiquitinating enzyme previously implicated in intellectual disability and autism spectrum disorder. Although these findings link USP6 to higher brain function, potential roles for USP6 in cognition have not been investigated. Here, we report that USP6 is highly expressed in induced human neurons and that neuron-specific expression of USP6 enhances learning and memory in a transgenic mouse model. Similarly, USP6 expression regulates N-methyl-D-aspartate-type glutamate receptor (NMDAR)-dependent long-term potentiation and long-term depression in USP6 transgenic mouse hippocampi. Proteomic characterization of transgenic USP6 mouse cortex reveals attenuated NMDAR ubiquitination, with concomitant elevation in NMDAR expression, stability, and cell surface distribution with USP6 overexpression. USP6 positively modulates GluN1 expression in transfected cells, and USP6 down-regulation impedes focal GluN1 distribution at postsynaptic densities and impairs synaptic function in neurons derived from human embryonic stem cells. Together, these results indicate that USP6 enhances NMDAR stability to promote synaptic function and cognition.
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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.