ArticleScientific reports2021
Deleting a UBE3A substrate rescues impaired hippocampal physiology and learning in Angelman syndrome mice.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Members of the RhoA subfamily of GTPases suppress the stimulatory effect of the HPV E6 oncoprotein on the ubiquitin ligase E6AP.Scientific reports · 2026Article
- Operant behavior is reliably impaired in a mouse model of Angelman syndrome.Research square · 2026Article
- Extracellular vesicle dysfunction contributes to synaptic and cognitive deficits in a mouse model of Angelman syndrome.Progress in neurobiology · 2026Article
- Extracellular Vesicles in Angelman Syndrome: Expanding UBE3A Role beyond a Cell Autonomous Mechanism.Journal of experimental neurology · 2026Article
- E3 ubiquitin ligases in signaling, disease, and therapeutics.Trends in biochemical sciences · 2025Review
- Activity-dependent degradation of Kv4.2 contributes to synaptic plasticity and behavior in Angelman syndrome model mice.Cell reports · 2025Article
- Activity-dependent regulation of Cdc42 by Ephexin5 drives synapse growth and stabilization.Science advances · 2025Article
- Unraveling the Roles of UBE3A in Neurodevelopment and Neurodegeneration.International journal of molecular sciences · 2025Review
- Understanding ubiquitination in neurodevelopment by integrating insights across space and time.Nature structural & molecular biology · 2025Review
- Crucial role of Snf7-3 in synaptic function and cognitive behavior revealed by conventional and conditional knockout mouse models.Neuroscience · 2024Article
- Ubiquitin system mutations in neurological diseases.Trends in biochemical sciences · 2024Review
- Neuronal UBE3A substrates hold therapeutic potential for Angelman syndrome.Current opinion in neurobiology · 2024Review
- Sex-biasing influence of autism-associatedScience advances · 2024Article
- UBE3A: The Role in Autism Spectrum Disorders (ASDs) and a Potential Candidate for Biomarker Studies and Designing Therapeutic Strategies.Diseases (Basel, Switzerland) · 2023Review
- Cntnap2-dependent molecular networks in autism spectrum disorder revealed through an integrative multi-omics analysis.Molecular psychiatry · 2023Article
- Activity-regulated E3 ubiquitin ligase TRIM47 modulates excitatory synapse development.Frontiers in molecular neuroscience · 2022Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
In humans, loss-of-function mutations in the UBE3A gene lead to the neurodevelopmental disorder Angelman syndrome (AS). AS patients have severe impairments in speech, learning and memory, and motor coordination, for which there is currently no treatment. In addition, UBE3A is duplicated in > 1-2% of patients with autism spectrum disorders-a further indication of the significant role it plays in brain development. Altered expression of UBE3A, an E3 ubiquitin ligase, is hypothesized to lead to impaired levels of its target proteins, but identifying the contribution of individual UBE3A targets to UBE3A-dependent deficits remains of critical importance. Ephexin5 is a putative UBE3A substrate that has restricted expression early in development, regulates synapse formation during hippocampal development, and is abnormally elevated in AS mice, modeled by maternally-derived Ube3a gene deletion. Here, we report that Ephexin5 can be directly ubiquitylated by UBE3A. Furthermore, removing Ephexin5 from AS mice specifically rescued hippocampus-dependent behaviors, CA1 physiology, and deficits in dendritic spine number. Our findings identify Ephexin5 as a key driver of hippocampal dysfunction and related behavioral deficits in AS mouse models. These results demonstrate the exciting potential of targeting Ephexin5, and possibly other UBE3A substrates, to improve symptoms of AS and other UBE3A-related developmental disorders.
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