The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
γCaMKII Shuttles Ca2+/CaM to the Nucleus to Trigger CREB Phosphorylation and Gene Expression
Open accessAbstract
SUMMARY 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 novel mechanism that mediates long-distance communication within cells: a shuttle that transports Ca2+/calmodulin from the surface membrane to the nucleus. We show that the shuttle protein is γCaMKII, that its phosphorylation at Thr287 by βCaMKII protects the Ca2+/CaM signal, and that CaN triggers its nuclear translocation. Both βCaMKII and CaN act in close proximity to CaV1 channels, supporting their dominance, while γCaMKII operates as a carrier, not as a kinase. Upon arrival within the nucleus, Ca2+/CaM activates CaMKK and its substrate CaMKIV, the CREB kinase. This mechanism resolves longstanding 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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Transcriptomic Analysis of Autistic Brain Reveals Convergent Molecular Pathology
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CaMKII: a central molecular organizer of synaptic plasticity, learning and memory
Yasuda, R., Hayashi, Y., & Hell, J. W. (2022) · Nature Reviews Neuroscience · doi:10.1038/s41583-022-00624-2 · Cited by 431
Lisman, J., Cooper, K., Sehgal, M., & Silva, A. J. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0076-6 · Cited by 351
Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications
Jiang, C.-C., Lin, L.-S., Long, S., Ke, X.-Y., Fukunaga, K., Lu, Y.-M., & Han, F. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01081-0 · Cited by 258
Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops
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Metadata
- Authors
- Ma, H., Groth, R. D., Cohen, S. M., Emery, J. F., Li, B., Hoedt, E., Zhang, G., Neubert, T. A., & Tsien, R. W.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 159
- Issue
- 2
- Pages
- 281-294
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2148129999
- Cited by
- 277
- References
- 18
- FWCI
- 8.15
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Ma, H., Groth, R. D., Cohen, S. M., Emery, J. F., Li, B., Hoedt, E., Zhang, G., Neubert, T. A., & Tsien, R. W. (2014). γCaMKII Shuttles Ca2+/CaM to the Nucleus to Trigger CREB Phosphorylation and Gene Expression. Cell. https://doi.org/10.1016/j.cell.2014.09.019
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