The DOI matches its Crossref record; 66 of the 67 references it cites were found in a registry or an index.
Reciprocal Activation within a Kinase-Effector Complex Underlying Persistence of Structural LTP
Open accessAbstract
Long-term synaptic plasticity requires a mechanism that converts short Ca 2+ pulses into persistent biochemical signaling to maintain changes in the synaptic structure and function. Here, we present a novel mechanism of a positive feedback loop, formed by a reciprocally activating kinase-effector complex (RAKEC) in dendritic spines, enabling the persistence and confinement of a molecular memory. We found that stimulation of a single spine causes the rapid formation of a RAKEC consisting of CaMKII and Tiam1, a Rac-GEF. This interaction is mediated by a pseudo-autoinhibitory domain on Tiam1, which is homologous to the CaMKII autoinhibitory domain itself. Therefore, Tiam1 binding results in constitutive CaMKII activation, which in turn persistently phosphorylates Tiam1. Phosphorylated Tiam1 promotes stable actin-polymerization through Rac1, thereby maintaining the structure of the spine during LTP. The RAKEC can store biochemical information in small subcellular compartments, thus potentially serving as a general mechanism for prolonged and compartmentalized signaling.
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“The authors find that Tiam1 has a CaMKII binding domain. This domain is homologous to the GluN2B CTD, and thus the Tiam1-CaMKII complex formation results in constitutive CaMKII activity.”
From Synaptic memory and CaMKII (2023) · cites this paper as [314]
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“The RhoGEFs that have received the most attention are kalirin-7, Trio, and Tiam, which are all expressed in spines and phosphorylated by CaMKII (314–317).”
From Synaptic memory and CaMKII (2023) · cites this paper as [314]
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In the citing paper
“CaMKII, in turn, phosphorylates Tiam1.”
From Synaptic memory and CaMKII (2023) · cites this paper as [314]
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“Indeed, there is compelling evidence that CaMKII, via phosphorylation, initiates a series of actin-based cytoskeletal rearrangements in the spine (32, 312–314).”
From Synaptic memory and CaMKII (2023) · cites this paper as [314]
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Cites
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 29,915
Germline Transmission and Tissue-Specific Expression of Transgenes Delivered by Lentiviral Vectors
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The molecular basis of CaMKII function in synaptic and behavioural memory
Lisman, J., Schulman, H., & Cline, H. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn753 · Cited by 1,860
The Conformational Plasticity of Protein Kinases
Huse, M., & Kuriyan, J. (2002) · Cell · doi:10.1016/s0092-8674(02)00741-9 · Cited by 1,760
Emergent Properties of Networks of Biological Signaling Pathways
Bhalla, U. S., & Iyengar, R. (1999) · Science · doi:10.1126/science.283.5400.381 · Cited by 1,686
Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation
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The Postsynaptic Architecture of Excitatory Synapses: A More Quantitative View
Sheng, M., & Hoogenraad, C. C. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.060805.160029 · Cited by 1,003
Okamoto, K.-I., Nagai, T., Miyawaki, A., & Hayashi, Y. (2004) · Nature Neuroscience · doi:10.1038/nn1311 · Cited by 854
Self-citationA Brief History of Long-Term Potentiation
Nicoll, R. A. (2017) · Neuron · doi:10.1016/j.neuron.2016.12.015 · Cited by 841
Interaction with the NMDA receptor locks CaMKII in an active conformation
Bayer, K.-U., De Koninck, P., Leonard, A. S., Hell, J. W., & Schulman, H. (2001) · Nature · doi:10.1038/35081080 · Cited by 732
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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
Self-citationCaM Kinase: Still Inspiring at 40
Bayer, K. U., & Schulman, H. (2019) · Neuron · doi:10.1016/j.neuron.2019.05.033 · Cited by 314
Spine dynamics in the brain, mental disorders and artificial neural networks
Kasai, H., Ziv, N. E., Okazaki, H., Yagishita, S., & Toyoizumi, T. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00467-3 · Cited by 184
NMDA receptor functions in health and disease: Old actor, new dimensions
Dupuis, J. P., Nicole, O., & Groc, L. (2023) · Neuron · doi:10.1016/j.neuron.2023.05.002 · Cited by 175
CaMKII activation persistently segregates postsynaptic proteins via liquid phase separation
Hosokawa, T., Liu, P.-W., Cai, Q., Ferreira, J. S., Levet, F., Butler, C., Sibarita, J.-B., Choquet, D., Groc, L., Hosy, E., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00843-3 · Cited by 146
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Metadata
- Authors
- Saneyoshi, T., Matsuno, H., Suzuki, A., Murakoshi, H., Hedrick, N. G., Agnello, E., O’Connell, R., Stratton, M. M., Yasuda, R., & Hayashi, Y.
- Affiliations
- Kyoto University (JP)
- RIKEN Center for Brain Science (JP)
- Max Planck Florida Institute for Neuroscience (US)
- Duke University (US)
- University of Massachusetts Amherst (US)
- South China Normal University (CN)
- Corresponding author
- Saneyoshi, Takeo
- Hayashi, Yasunori
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 102
- Issue
- 6
- Pages
- 1199-1210.e6
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC6669903
- OpenAlex
- W2944452573
- Cited by
- 119
- References
- 67
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 26 · 2023: 19 · 2022: 14 · 2021: 21 · 2020: 14 · 2019: 5
- FWCI
- 6.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Tokyo Tech Research Repository (Tokyo Institute of Technology) (submittedVersion)
- Funders
- Kyoto University Education and Research Foundation
- Human Frontier Science Program
- NOVARTIS Foundation (Japan) for the Promotion of Science
- Ministry of Education, Culture, Sports, Science and Technology (374539, 18H04733, 22110006, 817144, 20240032, 1031691, 854508, 16H02455, 18H05434)
- Takeda Science Foundation
- RIKEN
- Takeda Pharmaceutical Company
- Japan Foundation for Applied Enzymology
- Naito Foundation
- Brain Science Foundation
- Research Foundation for Opto-Science and Technology
- National Institutes of Health (R01DA17310, DP1-NS096787, R01-MH080047)
- Uehara Memorial Foundation
- Fujitsu
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- long-term potentiation, dendritic spines, CaMKII, Tiam1, positive feedback loop, actin polymerization, Rac1, synaptic plasticity, molecular memory, compartmentalized signaling
- MeSH terms
- T-Lymphoma Invasion and Metastasis-inducing Protein 1, Actins, Animals, Hippocampus, Neurons, Phosphorylation, Pyrones, Quinolines, Long-Term Potentiation, Microscopy, Confocal, Guanine Nucleotide Exchange Factors, rac1 GTP-Binding Protein, Feedback, Physiological, Dendritic Spines, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Polymerization
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