PT - JOURNAL ARTICLE AU - Randall S. Walikonis AU - Asako Oguni AU - Eugenia M. Khorosheva AU - Chung-Jiuan Jeng AU - Franklin J. Asuncion AU - Mary B. Kennedy TI - Densin-180 Forms a Ternary Complex with the α-Subunit of Ca<sup>2+</sup>/Calmodulin-Dependent Protein Kinase II and α-Actinin AID - 10.1523/JNEUROSCI.21-02-00423.2001 DP - 2001 Jan 15 TA - The Journal of Neuroscience PG - 423--433 VI - 21 IP - 2 4099 - http://www.jneurosci.org/content/21/2/423.short 4100 - http://www.jneurosci.org/content/21/2/423.full SO - J. Neurosci.2001 Jan 15; 21 AB - 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 Ca2+/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 EC50 of &gt;1 μm to an EC50 of &lt;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.