ArticleeLife2018
UBE3A-mediated p18/LAMTOR1 ubiquitination and degradation regulate mTORC1 activity and synaptic plasticity.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 59 citations in OpenAlex.
- UBE3A Inhibits Trophoblast Cell Migration and Invasion by Promoting ITGB1 Degradation and Affecting PI3K/AKT Signaling.The Kaohsiung journal of medical sciences · 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
- Dysfunction of the Autophagy System and MDM2-p53 Axis Leads to the Accumulation of Amyloidogenic Proteins in Angelman Syndrome Models.International journal of molecular sciences · 2025Article
- Loss of UBE3A impacts both neuronal and non-neuronal cells in human cerebral organoids.Communications biology · 2025Article
- Prenatal Exposure to Azadiradione Leads to Developmental Disabilities.Molecular neurobiology · 2025Article
- Impaired macroautophagy confers substantial risk for intellectual disability in children with autism spectrum disorders.Molecular psychiatry · 2025Article
- Ubiquitin-Proteasome-Mediated Protein Degradation and Disorders of the Central Nervous System.International journal of molecular sciences · 2025Review
- Alterations of synaptic plasticity in Angelman syndrome model mice are rescued by 5-HT7R stimulation.Progress in neurobiology · 2024Article
- Neuronal UBE3A substrates hold therapeutic potential for Angelman syndrome.Current opinion in neurobiology · 2024Review
- Fasting-induced RNF152 resensitizes gallbladder cancer cells to gemcitabine by inhibiting mTORC1-mediated glycolysis.iScience · 2024Article
- TRAF4-Mediated LAMTOR1 Ubiquitination Promotes mTORC1 Activation and Inhibits the Inflammation-Induced Colorectal Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- LAMTOR1 regulates dendritic lysosomal positioning in hippocampal neurons through TRPML1 inhibition.Frontiers in cellular neuroscience · 2024Article
- UBE3A: The Role in Autism Spectrum Disorders (ASDs) and a Potential Candidate for Biomarker Studies and Designing Therapeutic Strategies.Diseases (Basel, Switzerland) · 2023Review
- Contextual fear memory impairment in Angelman syndrome model mice is associated with altered transcriptional responses.Scientific reports · 2023Article
- Effects of UBE3A on the insulin resistance in polycystic ovary syndrome through the ubiquitination of AMPK.BMC endocrine disorders · 2023Article
- TBK1 Knockdown Alleviates Axonal Transport Deficits in Retinal Ganglion Cells Via mTORC1 Activation in a Retinal Damage Mouse Model.Investigative ophthalmology & visual science · 2023Article
- Blood RNA transcripts reveal similar and differential alterations in fundamental cellular processes in Alzheimer's disease and other neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- The Ragulator complex: delving its multifunctional impact on metabolism and beyond.Inflammation and regeneration · 2023Review
- UBE3A deficiency-induced autophagy is associated with activation of AMPK-ULK1 and p53 pathways.Experimental neurology · 2023Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Accumulating evidence indicates that the lysosomal Ragulator complex is essential for full activation of the mechanistic target of rapamycin complex 1 (mTORC1). Abnormal mTORC1 activation has been implicated in several developmental neurological disorders, including Angelman syndrome (AS), which is caused by maternal deficiency of the ubiquitin E3 ligase UBE3A. Here we report that Ube3a regulates mTORC1 signaling by targeting p18, a subunit of the Ragulator. Ube3a ubiquinates p18, resulting in its proteasomal degradation, and Ube3a deficiency in the hippocampus of AS mice induces increased lysosomal localization of p18 and other members of the Ragulator-Rag complex, and increased mTORC1 activity. p18 knockdown in hippocampal CA1 neurons of AS mice reduces elevated mTORC1 activity and improves dendritic spine maturation, long-term potentiation (LTP), as well as learning performance. Our results indicate that Ube3a-mediated regulation of p18 and subsequent mTORC1 signaling is critical for typical synaptic plasticity, dendritic spine development, and learning and memory.
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