ArticleThe Journal of cell biology2024
Nedd4-2-dependent regulation of astrocytic Kir4.1 and Connexin43 controls neuronal network activity.
Article in The Journal of cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Neuroligin-2 is ubiquitinated by Nedd4l to control developmental astrocyte morphogenesis.The Journal of cell biology · 2026Article
- When neuroligin-2 sticks around, astrocytes take shape.The Journal of cell biology · 2026Article
- Calponin-3 is associated with epilepsy through the regulation of astrocyte activity.Brain pathology (Zurich, Switzerland) · 2026Article
- Neuroligin-2 is ubiquitinated by Nedd4l to control developmental astrocyte morphogenesis.bioRxiv : the preprint server for biology · 2025Article
- The Double-Edged Effect of Connexins and Pannexins of Glial Cells in Central and Peripheral Nervous System After Nerve Injury.Molecular neurobiology · 2025Review
- Astrocytic Connexin43 Channels Are Essential for Breathing Pattern Stabilization in the preBötzinger Complex.CNS neuroscience & therapeutics · 2025Article
- TREK-1 and epilepsy: regulating the balance of KBehavioral and brain functions : BBF · 2025Review
- Research progress of connexins in epileptogensis.Acta epileptologica · 2025Review
- Preclinical Insights into the Role of Kir4.1 in Chronic Pain and Depression: Mechanisms and Therapeutic Potential.Biomolecules · 2025Review
- Nedl1 knockout ameliorates cognitive impairment and improves epilepsy threshold in pilocarpine-induced epileptic mice.Acta epileptologica · 2025Article
- Understanding ubiquitination in neurodevelopment by integrating insights across space and time.Nature structural & molecular biology · 2025Review
- The E3 ubiquitin ligase ITCH negatively regulates intercellular communication via gap junctions by targeting connexin43 for lysosomal degradation.Cellular and molecular life sciences : CMLS · 2024Article
Corrections and comments
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Authors and funding
30 authors at 9 institutions in 5 countries.
Funding
Abstract
Nedd4-2 is an E3 ubiquitin ligase in which missense mutation is related to familial epilepsy, indicating its critical role in regulating neuronal network activity. However, Nedd4-2 substrates involved in neuronal network function have yet to be identified. Using mouse lines lacking Nedd4-1 and Nedd4-2, we identified astrocytic channel proteins inwardly rectifying K+ channel 4.1 (Kir4.1) and Connexin43 as Nedd4-2 substrates. We found that the expression of Kir4.1 and Connexin43 is increased upon conditional deletion of Nedd4-2 in astrocytes, leading to an elevation of astrocytic membrane ion permeability and gap junction activity, with a consequent reduction of γ-oscillatory neuronal network activity. Interestingly, our biochemical data demonstrate that missense mutations found in familial epileptic patients produce gain-of-function of the Nedd4-2 gene product. Our data reveal a process of coordinated astrocytic ion channel proteostasis that controls astrocyte function and astrocyte-dependent neuronal network activity and elucidate a potential mechanism by which aberrant Nedd4-2 function leads to epilepsy.
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Registered trials
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