ArticleCell2014
γCaMKII shuttles Ca²⁺/CaM to the nucleus to trigger CREB phosphorylation and gene expression.
Article in Cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers, 1 of them a synthesis that pooled it.
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Who cites it
174 citing papers in PubMed, 1 synthesis or guideline pooled it, 278 citations in OpenAlex.
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- Regulation of chromatin dynamics by a calcium-dependent nucleoskeleton.The Journal of biological chemistry · 2026Article
- Effects of increasing intranuclear calcium levels via MCU inhibition on mouse and human PSC-derived cardiomyocyte differentiation and maturation.Stem cells translational medicine · 2026Article
- CaMKII as a Multimodal Signalling Hub in Neural Connectivity and Vulnerability.Molecular neurobiology · 2026Review
- Homeostatic preservation of action potential waveform by Notch and Nerfin-1.Current biology : CB · 2026Article
- Piezo1 Regulates ZnT1-Mediated Zinc Homeostasis in Ulcerative Colitis.Inflammation · 2026Article
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- Epigenetic Mechanisms Shaping Spine Regulation: Unveiling the Role of Cytoskeletal Dynamics and Localized Protein Synthesis.Molecular neurobiology · 2025Review
- Nuclear CaMKII Isoforms as Regulators of Transcription: From Developmental to Pathological Persistence.Medical sciences (Basel, Switzerland) · 2025Review
- Synaptic Plasticity-Enhancing and Cognitive-Improving Effects of Standardized Ethanol Extract ofInternational journal of molecular sciences · 2025Article
- Structure of a polymorphic repeat at theProceedings of the National Academy of Sciences of the United States of America · 2025Article
- CaMKII clusters neuronal LTCCs in biomolecular condensates to gate excitation-transcription coupling.bioRxiv : the preprint server for biology · 2025Article
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- Identification and Characterization of a Leoligin-Inspired Synthetic Lignan as a TGR5 Agonist.Journal of natural products · 2025Article
- Inter-organelle communication dynamically orchestrates juvenile hormone biosynthesis and female reproduction.National science review · 2025Article
114 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Activity-dependent CREB phosphorylation and gene expression are critical for long-term neuronal plasticity. Local signaling at CaV1 channels triggers these events, but how information is relayed onward to the nucleus remains unclear. Here, we report a mechanism that mediates long-distance communication within cells: a shuttle that transports Ca(2+)/calmodulin from the surface membrane to the nucleus. We show that the shuttle protein is γCaMKII, its phosphorylation at Thr287 by βCaMKII protects the Ca(2+)/CaM signal, and CaN triggers its nuclear translocation. Both βCaMKII and CaN act in close proximity to CaV1 channels, supporting their dominance, whereas γCaMKII operates as a carrier, not as a kinase. Upon arrival within the nucleus, Ca(2+)/CaM activates CaMKK and its substrate CaMKIV, the CREB kinase. This mechanism resolves long-standing puzzles about CaM/CaMK-dependent signaling to the nucleus. The significance of the mechanism is emphasized by dysregulation of CaV1, γCaMKII, βCaMKII, and CaN in multiple neuropsychiatric disorders.
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Registered trials
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.