Walikonis, Randall S. and Oguni, Asako and Khorosheva, Eugenia M. and Jeng, Chung-Jiuan and Asuncion, Franklin J. and Kennedy, Mary B. (2001) Densin-180 forms a ternary complex with the α-subunit of Ca^(2+)/calmodulin-dependent protein kinase II and α-actinin. Journal of Neuroscience, 21 (2). pp. 423-433. ISSN 0270-6474. PMCID PMC6763799. doi:10.1523/JNEUROSCI.21-02-00423.2001. https://resolver.caltech.edu/CaltechAUTHORS:20120424-150007753
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Abstract
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.
Item Type: | Article | ||||||||||
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Additional Information: | © 2001 Society for Neuroscience. Received Sept. 18, 2000; revised Oct. 20, 2000; accepted Oct. 30, 2000. This work was supported by National Institutes of Health Grants NS28710 and NS17660 (M.B.K.) and by a fellowship from the FRAXA (Fragile-X) Research Foundation (R.S.W.) and from the John Douglas French Alzheimer’s Foundation (C.-J.J.). | ||||||||||
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Subject Keywords: | postsynaptic density; synaptic plasticity; protein phosphorylation; synapse; spine; neuronal cytoskeleton | ||||||||||
Issue or Number: | 2 | ||||||||||
PubMed Central ID: | PMC6763799 | ||||||||||
DOI: | 10.1523/JNEUROSCI.21-02-00423.2001 | ||||||||||
Record Number: | CaltechAUTHORS:20120424-150007753 | ||||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20120424-150007753 | ||||||||||
Official Citation: | Densin-180 Forms a Ternary Complex with the α-Subunit of Ca2+/Calmodulin-Dependent Protein Kinase II and α-Actinin. Randall S. Walikonis, Asako Oguni, Eugenia M. Khorosheva, Chung-Jiuan Jeng, Franklin J. Asuncion, Mary B. Kennedy. Journal of Neuroscience 15 January 2001, 21 (2) 423-433; DOI: 10.1523/JNEUROSCI.21-02-00423.2001 | ||||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||
ID Code: | 30308 | ||||||||||
Collection: | CaltechAUTHORS | ||||||||||
Deposited By: | Melanie Stefan | ||||||||||
Deposited On: | 24 Apr 2012 22:32 | ||||||||||
Last Modified: | 09 Nov 2021 19:45 |
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