Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published January 15, 2001 | Published
Journal Article Open

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


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.

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.).

Attached Files

Published - 423.full.pdf


Files (723.8 kB)
Name Size Download all
723.8 kB Preview Download

Additional details

August 21, 2023
August 21, 2023