ArticleCell death and differentiation2023
KCTD13-mediated ubiquitination and degradation of GluN1 regulates excitatory synaptic transmission and seizure susceptibility.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- LncPTEC mediated homocysteine accumulation elevates oxidative stress via UBQLN1-dependent MTHFD1 ubiquitination in DKD.Cell death & disease · 2026Article
- Enhanced Glycolysis-Driven Histone H3K18 Lactylation Regulates Epileptogenesis by Modulating the E3 Ubiquitin Ligase COP1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A Global Analysis of the Complex Structural Organization of KCTD Proteins and Their Functional Implications.International journal of molecular sciences · 2026Review
- Review
- Multiomic insights into the MPO-mediated NET formation pathway in alcohol-induced epilepsy risk.Genes & diseases · 2026Article
- Clinical spectrum and treatment responses in.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- DIRAS2 modulates MAPK pathway-mediated ferroptosis to regulate excitation/inhibition balance and seizure susceptibility.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- HSDL2 Suppresses Epileptic Seizures Through Phosphorylation-Dependent Modulation of the PSD95-NMDAR Signaling Axis.CNS neuroscience & therapeutics · 2026Article
- Dihydroartemisinin Alleviates Neuronal Damage and Seizures in Epileptic Mice by Inhibiting Ferroptosis via the SIRT1/FOXO1/SLC7A11/GPX4 Pathway.CNS neuroscience & therapeutics · 2026Article
- Protein S-acylation: Pathological mechanisms and novel therapeutic targets for diabetic complications.Chinese herbal medicines · 2026Review
- Permethrin induces epileptic susceptibility via activation of NaCommunications biology · 2025Article
- Cullin-RING Ubiquitin Ligases in Neurodevelopment and Neurodevelopmental Disorders.Biomedicines · 2025Review
- Regulation of Synaptic NMDA Receptor Activity by Post-Translational Modifications.Neurochemical research · 2025Review
- A Hypothesis: Metabolic Contributions to 16p11.2 Deletion Syndrome.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Androgen receptor ubiquitination links KCTD13 to genitourinary tract defects.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- CPEB3 can regulate seizure susceptibility by inhibiting the transcriptional activity of STAT3 on NMDARs expression.Molecular medicine (Cambridge, Mass.) · 2025Article
- NMDA Receptors Coordinate Metabolic Reprogramming and Mitophagy in Schwann Cells to Promote Peripheral Nerve Regeneration.Research (Washington, D.C.) · 2025Article
- The pleiotropic spectrum of proximal 16p11.2 CNVs.American journal of human genetics · 2024Review
- Progress towards understanding risk factor mechanisms in the development of autism spectrum disorders.Biochemical Society transactions · 2024Review
- Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Temporal lobe epilepsy (TLE) is the most common and severe form of epilepsy in adults; however, its underlying pathomechanisms remain elusive. Dysregulation of ubiquitination is increasingly recognized to contribute to the development and maintenance of epilepsy. Herein, we observed for the first time that potassium channel tetramerization domain containing 13 (KCTD13) protein, a substrate-specific adapter for cullin3-based E3 ubiquitin ligase, was markedly down-regulated in the brain tissue of patients with TLE. In a TLE mouse model, the protein expression of KCTD13 dynamically changed during epileptogenesis. Knockdown of KCTD13 in the mouse hippocampus significantly enhanced seizure susceptibility and severity, whereas overexpression of KCTD13 showed the opposite effect. Mechanistically, GluN1, an obligatory subunit of N-methyl-D-aspartic acid receptors (NMDARs), was identified as a potential substrate protein of KCTD13. Further investigation revealed that KCTD13 facilitates lysine-48-linked polyubiquitination of GluN1 and its degradation through the ubiquitin-proteasome pathway. Besides, the lysine residue 860 of GluN1 is the main ubiquitin site. Importantly, dysregulation of KCTD13 affected membrane expression of glutamate receptors and impaired glutamate synaptic transmission. Systemic administration of the NMDAR inhibitor memantine significantly rescued the epileptic phenotype aggravated by KCTD13 knockdown. In conclusion, our results demonstrated an unrecognized pathway of KCTD13-GluN1 in epilepsy, suggesting KCTD13 as a potential neuroprotective therapeutic target for epilepsy.
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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.