Multivalent Interactions of Calcium/Calmodulin-dependent Protein Kinase II with the Postsynaptic Density Proteins NR2B, Densin-180, and α-Actinin-2
Open accessAbstract
Dendritic calcium/calmodulin-dependent protein kinase II (CaMKII) is dynamically targeted to the synapse. We show that CaMKIIalpha is associated with the CaMKII-binding proteins densin-180, the N-methyl-D-aspartate receptor NR2B subunit, and alpha-actinin in postsynaptic density-enriched rat brain fractions. Residues 819-894 within the C-terminal domain of alpha-actinin-2 constitute the minimal CaMKII-binding domain. Similar amounts of Thr286-autophosphorylated CaMKIIalpha holoenzyme [P-T286]CaMKII bind to alpha-actinin-2 as bind to NR2B (residues 1260-1339) or to densin-180 (residues 1247-1495) in glutathione-agarose cosedimentation assays, even though the CaMKII-binding domains share no amino acid sequence similarity. Like NR2B, alpha-actinin-2 binds to representative splice variants of each CaMKII gene (alpha, beta, gamma, and delta), whereas densin-180 binds selectively to CaMKIIalpha. In addition, C-terminal truncated CaMKIIalpha monomers can interact with NR2B and alpha-actinin-2, but not with densin-180. Soluble alpha-actinin-2 does not compete for [P-T286]CaMKII binding to immobilized densin-180 or NR2B. However, soluble densin-180, but not soluble NR2B, increases CaMKII binding to immobilized alpha-actinin-2 by approximately 10-fold in a PDZ domain-dependent manner. A His6-tagged NR2B fragment associates with GST-densin or GST-actinin but only in the presence of [P-T286]CaMKII. Similarly, His6-tagged densin-180 or alpha-actinin fragments associate with GST-NR2B in a…
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The CaMKII I205K mutation is expected to also disrupt binding to densin-180, α-actinin-2, and other PSD proteins.
“keeping in mind that this mutation is expected to also disrupt the binding to densin-180 and α-actinin-2 (234–236) and other PSD proteins.”
From Synaptic memory and CaMKII (2023) · cites this paper as [236]
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Neuronal L-Type Calcium Channel Signaling to the Nucleus Requires a Novel CaMKIIα-Shank3 Interaction
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- Authors
- Robison, A. J., Bass, M. A., Jiao, Y., MacMillan, L. B., Carmody, L. C., Bartlett, R. K., & Colbran, R. J.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Colbran, Roger J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 280
- Issue
- 42
- Pages
- 35329-35336
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2002380354
- Cited by
- 134
- References
- 3
- Citations by year
- 2026: 4 · 2025: 1 · 2023: 5 · 2022: 2 · 2020: 5 · 2019: 8 · 2018: 4 · 2017: 11 · 2016: 1 · 2015: 7 · 2014: 9 · 2013: 8 · 2012: 9
- FWCI
- 3.33
- 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, R01MH063232)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007563)
- National Institute of Neurological Disorders and Stroke (R01-NS44282)
- 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
- calcium/calmodulin-dependent protein kinase II, CaMKIIα, postsynaptic density, ACTN2, NR2B, NMDA receptor, PDZ domain, CaMKII autophosphorylation
- MeSH terms
- Actinin, Amino Acid Sequence, Animals, Glutathione, Glutathione Transferase, Histidine, Insecta, Male, Molecular Sequence Data, Mutation, Neurons, Phosphorylation, Protein Binding, Sepharose, Sialoglycoproteins, Swine, Synapses, Threonine, Xenopus, Blotting, Western, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Baculoviridae, Rats, Sprague-Dawley, Protein Structure, Tertiary, Calcium-Calmodulin-Dependent Protein Kinases, Protein Isoforms, Macromolecular Substances, Multiprotein Complexes, Immunoprecipitation, Mice, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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