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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

179 Scopus citations


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 (CaMKIlα), 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, Dlg, 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 >1 μm to an EC50 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.

Original languageEnglish
Pages (from-to)423-433
Number of pages11
JournalJournal of Neuroscience
Issue number2
StatePublished - 15 Jan 2001


  • Neuronal cytoskeleton
  • Postsynaptic density
  • Protein phosphorylation
  • Spine
  • Synapse
  • Synaptic plasticity


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