CaMKIIβ is localized in dendritic spines as both drebrin-dependent and drebrin-independent pools

Drebrin is a major F-actin binding protein in dendritic spines that is critically involved in the regulation of dendritic spine morphogenesis, pathology, and plasticity. In this study, we aimed to identify a novel drebrin-binding protein involved in spine morphogenesis and synaptic plasticity. We confirmed the beta subunit of Ca2+/calmodulin-dependent protein kinase II (CaMKII) as a drebrin-binding protein using a yeast two-hybrid system, and investigated the drebrin-CaMKII relationship in dendritic spines using rat hippocampal neurons. Drebrin knockdown resulted in diffuse localization of CaMKII in dendrites during the resting state, suggesting that drebrin is involved in the accumulation of CaMKII in dendritic spines. Fluorescence recovery after photobleaching analysis showed that drebrin knockdown increased the stable fraction of CaMKII, indicating the presence of drebrin-independent, more stable CaMKII. NMDA receptor activation also increased the stable fraction in parallel with drebrin exodus from dendritic spines. These findings suggest that CaMKII can be classified into distinct pools: CaMKII associated with drebrin, CaMKII associated with post-synaptic density (PSD), and CaMKII free from PSD and drebrin. CaMKII appears to be anchored to a protein complex composed of drebrin-binding F-actin during the resting state. NMDA receptor activation releases CaMKII from drebrin resulting in CaMKII association with PSD.