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Densin-180 forms a ternary complex with the α-subunit of Ca^(2+)/calmodulin-dependent protein kinase II and α-actinin

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. http://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
Related URLs:
URLURL TypeDescription
http://www.jneurosci.org/content/21/2/423PublisherUNSPECIFIED
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.).
Funders:
Funding AgencyGrant Number
NIHNS28710
NIHNS17660
FRAXA (Fragile-X) Research FoundationUNSPECIFIED
John Douglas French Alzheimer’s FoundationUNSPECIFIED
Subject Keywords:postsynaptic density; synaptic plasticity; protein phosphorylation; synapse; spine; neuronal cytoskeleton
Record Number:CaltechAUTHORS:20120424-150007753
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20120424-150007753
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:26 Dec 2012 15:07

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