ArticleBiological psychiatry2021
Neurogranin, Encoded by the Schizophrenia Risk Gene NRGN, Bidirectionally Modulates Synaptic Plasticity via Calmodulin-Dependent Regulation of the Neuronal Phosphoproteome.
Article in Biological psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 50 citations in OpenAlex.
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- Mapping genetic regulation of gene expression to cellular contexts identifies long non-coding RNAs associated with brain disorders.Nature communications · 2026Article
- High prevalence of CNS-directed autoantibodies in patients with schizophrenia.bioRxiv : the preprint server for biology · 2026Article
- Novel SLC16A2 mutations impair thyroid hormone transport and drive neurodevelopmental deficits in Chinese patients with allan-herndon-dudley syndrome.Scientific reports · 2026Article
- CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Context-tuned strategies for marker selection precision in neuronal studies.Frontiers in neuroscience · 2026Review
- Early-life gut microbiome maturity regulates blood-brain barrier and cognitive development.Gut microbes · 2025Article
- Systematic Analysis of SH-SY5Y Differentiation Protocols and Neuronal Subtype Abundance.Cellular and molecular neurobiology · 2025Article
- SCRIPT: Predicting Single-Cell Long-Range Cis-Regulation Based on Pretrained Graph Attention Networks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Cooperation of Neurogranin with Calmodulin Promotes the Treatment of Aging-Related Diseases via Regular Exercise.Molecular neurobiology · 2025Review
- Spatiomolecular mapping reveals anatomical organization of heterogeneous cell types in the human nucleus accumbens.bioRxiv : the preprint server for biology · 2025Article
- Common Genomic and Proteomic Alterations Related to Disturbed Neural Oscillatory Activity in Schizophrenia.International journal of molecular sciences · 2025Review
- Combined Exercise and Ursolic Acid Improve Hippocampal Neuronal Markers and Exploratory-Locomotor Behavior in Aged Diabetic Rats.Journal of aging research · 2025Article
- Repurposing major metabolites of lamiaceae family as potential inhibitors ofFrontiers in pharmacology · 2025Article
- Temporal-Specific Sex and Injury-Dependent Changes on Neurogranin-Associated Synaptic Signaling After Controlled Cortical Impact in Rats.Molecular neurobiology · 2024Article
- Genetic mechanisms for impaired synaptic plasticity in schizophrenia revealed by computational modeling.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Manganese Overexposure Alters Neurogranin Expression and Causes Behavioral Deficits in Larval Zebrafish.International journal of molecular sciences · 2024Article
- Ranking of cell clusters in a single-cell RNA-sequencing analysis framework using prior knowledge.PLoS computational biology · 2024Article
- The Association of Redox Regulatory Drug Target Genes with Psychiatric Disorders: A Mendelian Randomization Study.Antioxidants (Basel, Switzerland) · 2024Article
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundNeurogranin (Ng), encoded by the schizophrenia risk gene NRGN, is a calmodulin-binding protein enriched in the postsynaptic compartments, and its expression is reduced in the postmortem brains of patients with schizophrenia. Experience-dependent translation of Ng is critical for encoding contextual memory, and Ng regulates developmental plasticity in the primary visual cortex during the critical period. However, the overall impact of Ng on the neuronal signaling that regulates synaptic plasticity is unknown.
methodsAltered Ng expression was achieved via virus-mediated gene manipulation in mice. The effect on long-term potentiation (LTP) was accessed using spike timing-dependent plasticity protocols. Quantitative phosphoproteomics analyses led to discoveries in significant phosphorylated targets. An identified candidate was examined with high-throughput planar patch clamp and was validated with pharmacological manipulation.
resultsNg bidirectionally modulated LTP in the hippocampus. Decreasing Ng levels significantly affected the phosphorylation pattern of postsynaptic density proteins, including glutamate receptors, GTPases, kinases, RNA binding proteins, selective ion channels, and ionic transporters, some of which highlighted clusters of schizophrenia- and autism-related genes. Hypophosphorylation of NMDA receptor subunit Grin2A, one significant phosphorylated target, resulted in accelerated decay of NMDA receptor currents. Blocking protein phosphatase PP2B activity rescued the accelerated NMDA receptor current decay and the impairment of LTP mediated by Ng knockdown, implicating the requirement of synaptic PP2B activity for the deficits.
conclusionsAltered Ng levels affect the phosphorylation landscape of neuronal proteins. PP2B activity is required for mediating the deficit in synaptic plasticity caused by decreasing Ng levels, revealing a novel mechanistic link of a schizophrenia risk gene to cognitive deficits.
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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.