ArticleThe Journal of biological chemistry2016
Neuritin Up-regulates Kv4.2 α-Subunit of Potassium Channel Expression and Affects Neuronal Excitability by Regulating the Calcium-Calcineurin-NFATc4 Signaling Pathway.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- The Role of Neuritin 1 in Synaptic Plasticity and Sensory Nerve Function: Integrator of Neurotrophic, Metabolic and Injury Signals.The European journal of neuroscience · 2026Review
- Genetic Signatures of Competitive Performance in Burmese Gamecocks: A Transcriptomic Analysis.Biology · 2025Article
- Conditional Overexpression of Neuritin in Supporting Cell Protects Cochlear Hair Cell and Delays Age-Related Hearing Loss by Enhancing Autophagy.International journal of molecular sciences · 2025Article
- Neuritin: a multifaceted neuroprotective factor with emerging applications for neurodegeneration.Frontiers in neuroscience · 2025Review
- Neuritin Controls Axonal Branching in Serotonin Neurons: A Possible Mediator Involved in the Regulation of Depressive and Anxiety Behaviors via FGF Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Neuritin accelerates Schwann cell dedifferentiation via PI3K/Akt/mTOR signalling pathway during Wallerian degeneration.Journal of cellular and molecular medicine · 2024Article
- Design of Ultrapotent Genetically Encoded Inhibitors of Kv4.2 for Gating Neural Plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- LGI1 governs neuritin-mediated resilience to chronic stress.Neurobiology of stress · 2021Article
- Methylation of NRN1 is a novel synthetic lethal marker of PI3K-Akt-mTOR and ATR inhibitors in esophageal cancer.Cancer science · 2021Article
- Inhibition of Syk promotes chemical reprogramming of fibroblasts via metabolic rewiring and HThe EMBO journal · 2021Article
- Nrn1 Overexpression Attenuates Retinal Ganglion Cell Apoptosis, Promotes Axonal Regeneration, and Improves Visual Function Following Optic Nerve Crush in Rats.Journal of molecular neuroscience : MN · 2021Article
- Clinicopathological and Preclinical Patient-Derived Model Studies Define High Expression of NRN1 as a Diagnostic and Therapeutic Target for Clear Cell Renal Cell Carcinoma.Frontiers in oncology · 2021Article
- Cholinergic Synaptic Homeostasis Is Tuned by an NFAT-Mediated α7 nAChR-KCell reports · 2020Article
- CRISPR Interference-Based Platform for Multimodal Genetic Screens in Human iPSC-Derived Neurons.Neuron · 2019Article
- AMPA receptors and their minions: auxiliary proteins in AMPA receptor trafficking.Cellular and molecular life sciences : CMLS · 2019Review
- FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism.Nature communications · 2019Article
- A polybasic motif in alternatively spliced KChIP2 isoforms prevents CaThe Journal of biological chemistry · 2019Article
- Transcriptional Regulation of Channelopathies in Genetic and Acquired Epilepsies.Frontiers in cellular neuroscience · 2019Review
- Nfatc4 Deficiency Attenuates Ototoxicity by Suppressing Tnf-Mediated Hair Cell Apoptosis in the Mouse Cochlea.Frontiers in immunology · 2019Article
- Neuritin promotes neurite and spine growth in rat cerebellar granule cells via L-type calcium channel-mediated calcium influx.Journal of neurochemistry · 2018Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuritin is an important neurotrophin that regulates neural development, synaptic plasticity, and neuronal survival. Elucidating the downstream molecular signaling is important for potential therapeutic applications of neuritin in neuronal dysfunctions. We previously showed that neuritin up-regulates transient potassium outward current (IA) subunit Kv4.2 expression and increases IA densities, in part by activating the insulin receptor signaling pathway. Molecular mechanisms of neuritin-induced Kv4.2 expression remain elusive. Here, we report that the Ca(2+)/calcineurin (CaN)/nuclear factor of activated T-cells (NFAT) c4 axis is required for neuritin-induced Kv4.2 transcriptional expression and potentiation of IA densities in cerebellum granule neurons. We found that neuritin elevates intracellular Ca(2+) and increases Kv4.2 expression and IA densities; this effect was sensitive to CaN inhibition and was eliminated in Nfatc4(-/-) mice but not in Nfatc2(-/-) mice. Stimulation with neuritin significantly increased nuclear accumulation of NFATc4 in cerebellum granule cells and HeLa cells, which expressed IR. Furthermore, NFATc4 was recruited to the Kv4.2 gene promoter loci detected by luciferase reporter and chromatin immunoprecipitation assays. More importantly, data obtained from cortical neurons following adeno-associated virus-mediated overexpression of neuritin indicated that reduced neuronal excitability and increased formation of dendritic spines were abrogated in the Nfatc4(-/-) mice. Together, these data demonstrate an indispensable role for the CaN/NFATc4 signaling pathway in neuritin-regulated neuronal functions.
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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.