ArticlePLoS computational biology2020
Neurogranin stimulates Ca2+/calmodulin-dependent kinase II by suppressing calcineurin activity at specific calcium spike frequencies.
Article in PLoS computational biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Neurogranin and VILIP-1 as Molecular Indicators of Neurodegeneration in Alzheimer's Disease: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2020Pooled it
- Neurogranin Promotes Neuronal Maturation and Network Activity Through CaInternational journal of molecular sciences · 2026Article
- The Cooperation of Neurogranin with Calmodulin Promotes the Treatment of Aging-Related Diseases via Regular Exercise.Molecular neurobiology · 2025Review
- CaMK2rep: A Highly Sensitive Genetically Encoded Biosensor for Monitoring CaMKII Activity in Mammalian Cells.Analytical chemistry · 2025Article
- Endothelial Neurogranin Regulates Blood-Brain Barrier Permeability via Modulation of the AKT Pathway.Molecular neurobiology · 2025Article
- Temporospatial expression of neurogranin in the rat molar development.Journal of molecular histology · 2025Article
- Data Hazards as An Ethical Toolkit for Neuroscience.Neuroethics · 2025Article
- Protein Biomarkers Shared by Multiple Neurodegenerative Diseases Are Calmodulin-Binding Proteins Offering Novel and Potentially Universal Therapeutic Targets.Journal of clinical medicine · 2023Review
- Alzheimer's Disease beyond Calcium Dysregulation: The Complex Interplay between Calmodulin, Calmodulin-Binding Proteins and Amyloid Beta from Disease Onset through Progression.Current issues in molecular biology · 2023Review
- Emerging blood exosome-based biomarkers for preclinical and clinical Alzheimer's disease: a meta-analysis and systematic review.Neural regeneration research · 2022Review
- Neurogranin-like immunoreactivity in the zebrafish brain during development.Brain structure & function · 2022Article
- Evaluation of Synaptic and Axonal Dysfunction Biomarkers in Alzheimer's Disease and Mild Cognitive Impairment Based on CSF and Bioinformatic Analysis.International journal of molecular sciences · 2022Article
- Distribution of neurogranin-like immunoreactivity in the brain and sensory organs of the adult zebrafish.The Journal of comparative neurology · 2022Article
- The effects of neurogranin knockdown on SERCA pump efficiency in soleus muscles of female mice fed a high fat diet.Frontiers in endocrinology · 2022Article
- Calmodulin Binding Proteins and Alzheimer's Disease: Biomarkers, Regulatory Enzymes and Receptors That Are Regulated by Calmodulin.International journal of molecular sciences · 2020Review
- Article
- Computational Modeling Reveals Frequency Modulation of Calcium-cAMP/PKA Pathway in Dendritic Spines.Biophysical journal · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Calmodulin sits at the center of molecular mechanisms underlying learning and memory. Its complex and sometimes opposite influences, mediated via the binding to various proteins, are yet to be fully understood. Calcium/calmodulin-dependent protein kinase II (CaMKII) and calcineurin (CaN) both bind open calmodulin, favoring Long-Term Potentiation (LTP) or Depression (LTD) respectively. Neurogranin binds to the closed conformation of calmodulin and its impact on synaptic plasticity is less clear. We set up a mechanistic computational model based on allosteric principles to simulate calmodulin state transitions and its interactions with calcium ions and the three binding partners mentioned above. We simulated calcium spikes at various frequencies and show that neurogranin regulates synaptic plasticity along three modalities. At low spike frequencies, neurogranin inhibits the onset of LTD by limiting CaN activation. At intermediate frequencies, neurogranin facilitates LTD, but limits LTP by precluding binding of CaMKII with calmodulin. Finally, at high spike frequencies, neurogranin promotes LTP by enhancing CaMKII autophosphorylation. While neurogranin might act as a calmodulin buffer, it does not significantly preclude the calmodulin opening by calcium. On the contrary, neurogranin synchronizes the opening of calmodulin's two lobes and promotes their activation at specific frequencies. Neurogranin suppresses basal CaN activity, thus increasing the chance of CaMKII trans-autophosphorylation at high-frequency calcium spikes. Taken together, our study reveals dynamic regulatory roles played by neurogranin on synaptic plasticity, which provide mechanistic explanations for opposing experimental findings.
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