Densin-180 Forms a Ternary Complex with the α-Subunit of Ca2+/Calmodulin-Dependent Protein Kinase II and α-Actinin
Open accessAbstract
Densin-180 is a transmembrane protein that is tightly associated with the postsynaptic density in CNS neurons and is postulated to function as a synaptic adhesion molecule. Here we report the identification of the α-subunit of Ca 2+/calmodulin-dependent protein kinase II (CaMKII) and α-actinin-4 as potential binding partners for the densin-180 intracellular segment. We demonstrate by yeast two-hybrid and biochemical assays that the intracellular portion of densin-180, the α-subunit of CaMKII (CaMKIIα), and α-actinin interact with each other at distinct binding sites and can form a ternary complex stabilized by multiple interactions. Densin-180 binds specifically to the association domain of CaMKIIα and does not bind with high affinity to holoenzymes of CaMKII that contain β-subunit. The PDZ (PSD-95, DIg, Z0-1) domain of densin contributes to its binding to α-actinin. A distinct domain of α-actinin interacts with the kinase domains of both α- and β-subunits of CaMKII. Autophosphorylation of CaMKII increases its affinity for densin-180 from an EC 50 of >1 μm to an EC 50 of <75–150 nM. In contrast, phosphorylation of densin-180 by CaMKII at serine-1397 only slightly decreases its affinity for CaMKII. The specific interaction of densin-180 with holoenzymes of CaMKII containing only α-subunit and the increased affinity of CaMKII for densin-180 after autophosphorylation suggest that densin-180 may be involved in localization of activated CaMKII synthesized in dendrites.
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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 [235]
The Discussion reports that CaMKIIα binds densin-180 and α-actinin, but at distinct sites: densin binds its association domain, whereas α-actinin binds its kinase domain. The paper identifies α-actinin-4 as a binding partner, not α-actinin-2, and does not test the I205K mutation or establish that it disrupts binding to these or other PSD proteins. The reported interactions support only the background premise of the prediction. (LLM, conf=0.86)
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Cites
Competitive binding of α-actinin and calmodulin to the NMDA receptor
Wyszynski, M., Lin, J., Rao, A., Nigh, E., Beggs, A. H., Craig, A. M., & Sheng, M. (1997) · Nature · doi:10.1038/385439a0 · Cited by 596 · see citing works
Shen, K., Teruel, M. N., Subramanian, K., & Meyer, T. (1998) · Neuron · doi:10.1016/s0896-6273(00)80569-3 · Cited by 350 · see citing works
Allison, D. W., Chervin, A. S., Gelfand, V. I., & Craig, A. M. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-12-04545.2000 · Cited by 245 · see citing works
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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 · see citing works
Mechanisms of CaMKII action in long-term potentiation
Lisman, J., Yasuda, R., & Raghavachari, S. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3192 · Cited by 1,134 · see citing works
Okamoto, K.-I., Narayanan, R., Lee, S. H., Murata, K., & Hayashi, Y. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701656104 · Cited by 328 · see citing works
Synaptic Signaling in Learning and Memory
Kennedy, M. B. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016824 · Cited by 270 · see citing works
Self-citationAutophosphorylated CaMKIIα Acts as a Scaffold to Recruit Proteasomes to Dendritic Spines
Bingol, B., Wang, C.-F., Arnott, D., Cheng, D., Peng, J., & Sheng, M. (2010) · Cell · doi:10.1016/j.cell.2010.01.024 · Cited by 268 · see citing works
Otmakhov, N., Tao-Cheng, J.-H., Carpenter, S., Asrican, B., Dosemeci, A., Reese, T. S., & Lisman, J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.2350-04.2004 · Cited by 258 · see citing works
Long-term potentiation: outstanding questions and attempted synthesis
Lisman, J. (2003) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.2002.1242 · Cited by 240 · see citing works
Junctional recruitment of mammalian Scribble relies on E-cadherin engagement
Navarro, C., Nola, S., Audebert, S., Santoni, M.-J., Arsanto, J.-P., Ginestier, C., Marchetto, S., Jacquemier, J., Isnardon, D., Le Bivic, A., et al. (2005) · Oncogene · doi:10.1038/sj.onc.1208632 · Cited by 237 · see citing works
Nicoll, R. A., & Schulman, H. (2023) · Physiological Reviews · doi:10.1152/physrev.00034.2022 · Cited by 126 · see citing works
Reciprocal Activation within a Kinase-Effector Complex Underlying Persistence of Structural LTP
Saneyoshi, T., Matsuno, H., Suzuki, A., Murakoshi, H., Hedrick, N. G., Agnello, E., O’Connell, R., Stratton, M. M., Yasuda, R., & Hayashi, Y. (2019) · Neuron · doi:10.1016/j.neuron.2019.04.012 · Cited by 119 · see citing works
Ca2+-dependent modulation of voltage-gated Ca2+ channels
Christel, C., & Lee, A. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.12.012 · Cited by 112 · see citing works
Quitsch, A., Berhörster, K., Liew, C. W., Richter, D., & Kreienkamp, H.-J. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2699-04.2005 · Cited by 95 · see citing works
Carlisle, H. J., Luong, T. N., Medina-Marino, A., Schenker, L., Khorosheva, E., Indersmitten, T., Gunapala, K. M., Steele, A. D., O'Dell, T. J., Patterson, P. H., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.5877-10.2011 · Cited by 74 · see citing works
Self-citationDendritic spine actin cytoskeleton in autism spectrum disorder
Joensuu, M., Lanoue, V., & Hotulainen, P. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.08.023 · Cited by 65 · see citing works
Vessey, J. P., & Karra, D. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04662.x · Cited by 44 · see citing works
Activity-dependent redistribution of CaMKII in the postsynaptic compartment of hippocampal neurons
Tao-Cheng, J.-H. (2020) · Molecular Brain · doi:10.1186/s13041-020-00594-5 · Cited by 38 · see citing works
Gu, Z., Jiang, Q., Yuen, E. Y., & Yan, Z. (2006) · Molecular Pharmacology · doi:10.1124/mol.105.018853 · Cited by 35 · see citing works
- Authors
- Walikonis, R. S., Oguni, A., Khorosheva, E. M., Jeng, C.-J., Asuncion, F. J., & Kennedy, M. B.
- Affiliations
- California Institute of Technology (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-01-15
- Volume
- 21
- Issue
- 2
- Pages
- 423-433
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W4296759721
- Cited by
- 181
- References
- 3
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 7 · 2022: 3 · 2021: 5 · 2020: 16 · 2019: 4 · 2018: 6 · 2017: 6 · 2016: 5 · 2015: 3 · 2014: 5 · 2013: 3 · 2012: 9
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- FRAXA Research Foundation
- John Douglas French Alzheimer's Foundation
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS028710, R01NS017660, NS-17660, NS28710)
- 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
- ACTN4, ternary protein complex, postsynaptic density, synaptic adhesion molecules, PDZ domain, protein-protein interaction, autophosphorylation, dendrites
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