ArticleCell death & disease2019
PLPP/CIN-mediated NEDD4-2 S448 dephosphorylation regulates neuronal excitability via GluA1 ubiquitination.
Article in Cell death & disease, 2019. 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, 24 citations in OpenAlex.
- Nedd4L-mediated stabilization of morphogenetic protein receptor 2 in lung fibroblasts confers protection against pulmonary fibrosis.Signal transduction and targeted therapy · 2026Article
- Cannabinoid tolerance relies on CBProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Missense variant in TTBK2 kinase domain causes loss of function and impaired protein phosphorylation.Scientific reports · 2025Article
- Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain.Experimental neurology · 2024Review
- Novel KCNQ2 missense variant expands the genotype spectrum of DEE7.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Molecular Mechanisms of AMPA Receptor Trafficking in the Nervous System.International journal of molecular sciences · 2023Review
- Kinase Suppressor of RAS 1 (KSR1) Maintains the Transformed Phenotype of BRAFV600E Mutant Human Melanoma Cells.International journal of molecular sciences · 2023Article
- KCTD13-mediated ubiquitination and degradation of GluN1 regulates excitatory synaptic transmission and seizure susceptibility.Cell death and differentiation · 2023Article
- PLPP/CIN-mediated NF2 S10 dephosphorylation distinctly regulates kainate-induced seizure susceptibility and neuronal death through PAK1-NF-κB-COX-2-PTGES2 signaling pathway.Journal of neuroinflammation · 2023Article
- Infantile spasms-linked Nedd4-2 mediates hippocampal plasticity and learning via cofilin signaling.EMBO reports · 2021Article
- Historical perspective and progress on protein ubiquitination at glutamatergic synapses.Neuropharmacology · 2021Review
- AMPA Receptor Antagonists Facilitate NEDD4-2-Mediated GRIA1 Ubiquitination by Regulating PP2B-ERK1/2-SGK1 Pathway in Chronic Epilepsy Rats.Biomedicines · 2021Article
- Unbiased proteomic screening identifies a novel role for the E3 ubiquitin ligase Nedd4-2 in translational suppression during ER stress.Journal of neurochemistry · 2021Article
- PLPP/CIN-mediated NF2-serine 10 dephosphorylation regulates F-actin stability and Mdm2 degradation in an activity-dependent manner.Cell death & disease · 2021Article
- P2 × 7 Receptor Inhibits Astroglial Autophagy via Regulating FAK- and PHLPP1/2-Mediated AKT-S473 Phosphorylation Following Kainic Acid-Induced Seizures.International journal of molecular sciences · 2020Article
- Inhibition of USP15 Prevent Glutamate-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway in HT22 Cells.Cellular and molecular neurobiology · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuronal precursor cell expressed developmentally downregulated 4-2 (NEDD4-2) is an E3 ubiquitin ligase to regulate ion transport by controlling cellular trafficking/endocytosis and lysosomal degradation of ion channels and transporters. Thus, NEDD4-2 is relevant to neuronal excitability and epileptic encephalopathies in human patients. However, the regulatory molecules for NEDD4-2 dephosphorylation have been still elusive. Here, we demonstrate that pyridoxal-5'-phosphate phosphatase/chronophin (PLPP/CIN) specifically dephosphorylated NEDD4-2 serine (S) 448 site. PLPP/CIN deletion inhibited NEDD4-2 ubiquitination, and diminished the responsiveness of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) by facilitating NEDD4-2-mediated ubiquitination of GluA1 subunit under physiological condition. PLPP/CIN overexpression reversed these effects. These PLPP/CIN-mediated processes were required for the increased seizure severity and its progression in response to kainic acid (KA). Therefore, we suggest the novel function of PLPP/CIN as a NEDD4-2 phosphatase, which may be a potential therapeutic target for NEDD4-2-associated diseases as well as various neurological and psychiatric disorders, including epilepsy.
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