Super-resolution imaging reveals the relationship between CaMKIIß and drebrin within dendritic spines.

Dendritic spines are unique postsynaptic structures that emerge from the dendrites of neurons. They undergo activity-dependent morphological changes known as structural plasticity. The changes involve actin cytoskeletal remodeling, which is regulated by actin-binding proteins. CaMKII is a crucial molecule in synaptic plasticity. Notably, CaMKIIß subtype is known to bind to filamentous-actin and is closely involved in structural plasticity. We have shown that CaMKIIß binds to drebrin, and is localized in spines as both drebrin-dependent and drebrin-independent pools. However, the nanoscale relationship between drebrin and CaMKIIß within dendritic spines has not been clarified. In this study, we used stochastic optical reconstruction microscopy (STORM) to examine the detailed localization of these proteins. STORM imaging showed that CaMKIIß co-localized with drebrin in the core region of spines, and localized in the submembrane region of spines without drebrin. Interestingly, the dissociation of CaMKIIß and drebrin in the core region was induced by NMDA receptor activation. In drebrin knockdown neurons, CaMKIIß was decreased in the core region but not in the submembrane region. Together it indicates that the clustering of CaMKIIß in the spine core region is dependent on drebrin. These findings suggest that drebrin-dependent CaMKIIß is in a standby state before its activation.