Differential Modulation of Ca2+/Calmodulin-dependent Protein Kinase II Activity by Regulated Interactions with N-Methyl-D-aspartate Receptor NR2B Subunits and α-Actinin
Open accessAbstract
Neuronal Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) interacts with several prominent dendritic spine proteins, which have been termed CaMKII-associated proteins. The NR2B subunit of N-methyl-d-aspartate (NMDA)-type glutamate receptor, densin-180, and alpha-actinin bind comparable, approximately stoichiometric amounts of Thr(286)-autophosphorylated CaMKIIalpha, forming a ternary complex (Robison, A. J., Bass, M. A., Jiao, Y., Macmillan, L. B., Carmody, L. C., Bartlett, R. K., and Colbran, R. J. (2005) J. Biol. Chem. 280, 35329-35336), but their impacts on CaMKII function are poorly understood. Here we show that these interactions are differentially regulated and exert distinct effects on CaMKII activity. Nonphosphorylated and Thr(286)-autophosphorylated CaMKII bind to alpha-actinin with similar efficacy, but autophosphorylation at Thr(305/306) or Ca(2+)/calmodulin binding significantly reduce this binding. Moreover, alpha-actinin antagonizes CaMKII activation by Ca(2+)/calmodulin, as assessed by autophosphorylation and phosphorylation of a peptide substrate. CaMKII binding to densin (1247-1542) is partially independent of Thr(286) autophosphorylation and is unaffected by Ca(2+)-independent autophosphorylation or Ca(2+)/calmodulin. In addition, the CaMKII binding domain of densin-180 has little effect on CaMKII activity. In contrast, the interaction of CaMKIIalpha with NR2B requires either Thr(286) autophosphorylation or the binding of both Ca(2+)/calmodulin and ade…
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Simply adding CTD to a kinase reaction inhibits substrate phosphorylation.
“simply adding CTD to a kinase reaction produced an inhibition of substrate phosphorylation (118).”
From Synaptic memory and CaMKII (2023) · cites this paper as [118]
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- Authors
- Robison, A. J., Bartlett, R. K., Bass, M. A., & Colbran, R. J.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Colbran, Roger J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 280
- Issue
- 47
- Pages
- 39316-39323
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2061499765
- Cited by
- 84
- References
- 50
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 1 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 8 · 2013: 2 · 2012: 6
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (F32-MH068129, MH63232, R01MH063232)
- National Institute of Diabetes and Digestive and Kidney Diseases (5T32 DK07563, T32DK007563)
- National Institute of Neurological Disorders and Stroke (NS44082)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- CaMKII, NR2B subunit, alpha-actinin, CaMKII autophosphorylation, protein-protein interaction, dendritic spines, adenine nucleotides, ternary complex
- MeSH terms
- Actinin, Animals, Binding Sites, Calcium, Calmodulin, Kinetics, Models, Biological, Phosphorylation, Recombinant Fusion Proteins, Sialoglycoproteins, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Calcium-Calmodulin-Dependent Protein Kinases, Protein Subunits, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2, In Vitro Techniques
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