Calcium/calmodulin-dependent protein kinase II is associated with the N -methyl- d -aspartate receptor
Open accessAbstract
The molecular basis of long-term potentiation (LTP), a long-lasting change in synaptic transmission, is of fundamental interest because of its implication in learning. Usually LTP depends on Ca2+ influx through postsynaptic N-methyl-D-aspartate (NMDA)-type glutamate receptors and subsequent activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). For a molecular understanding of LTP it is crucial to know how CaMKII is localized to its postsynaptic targets because protein kinases often are targeted to their substrates by adapter proteins. Here we show that CaMKII directly binds to the NMDA receptor subunits NR1 and NR2B. Moreover, activation of CaMKIIalpha by stimulation of NMDA receptors in forebrain slices increase this association. This interaction places CaMKII not only proximal to a major source of Ca2+ influx but also close to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors, which become phosphorylated upon stimulation of NMDA receptors in these forebrain slices. Identification of the postsynaptic adapter for CaMKII fills a critical gap in the understanding of LTP because CaMKII-mediated phosphorylation of AMPA receptors is an important step during LTP.
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This translocation involves the binding of CaMKII to the NMDAR.
“This translocation involves the binding of CaMKII to the NMDAR (78, 125, 144, 221–224).”
From Synaptic memory and CaMKII (2023) · cites this paper as [144]
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- Authors
- Leonard, A. S., Lim, I. A., Hemsworth, D. E., Horne, M. C., & Hell, J. W.
- Affiliations
- University of Wisconsin System (US)
- University of Wisconsin–Madison (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-03-16
- Volume
- 96
- Issue
- 6
- Pages
- 3239-3244
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC15926
- OpenAlex
- W1997956229
- Cited by
- 385
- References
- 1
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 11 · 2023: 7 · 2022: 10 · 2021: 7 · 2020: 5 · 2019: 10 · 2018: 11 · 2017: 17 · 2016: 12 · 2015: 7 · 2014: 15 · 2013: 21 · 2012: 14
- FWCI
- 8.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- American Heart Association
- National Institutes of Health
- National Cancer Institute (P30CA086862)
- National Institute of General Medical Sciences (T32GM008692)
- National Institute of Neurological Disorders and Stroke (R01-NS35563, R01NS035563)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- CaMKII, NMDA receptor, long-term potentiation, NR1 subunit, NR2B subunit, AMPA receptor phosphorylation, synaptic plasticity, learning, adaptor proteins
- MeSH terms
- Animals, Brain, Synaptic Transmission, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Calcium-Calmodulin-Dependent Protein Kinases, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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