CaMKIIβ functions as an F-actin targeting module that localizes CaMKIIα/β heterooligomers to dendritic spines

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine protein kinase that regulates long-term potentiation and other forms of neuronal plasticity. Functional differences between the neuronal CaMKII alpha and CaMKII beta isoforms are not yet known. Here, we use green fluorescent protein-tagged (GFP-tagged) CaMKII isoforms and show that CaMKII beta is bound to F-actin in dendritic spines and cell cortex while CaMKII alpha is largely a cytosolic enzyme. When expressed together, the two isoforms form large heterooligomers, and a small fraction of CaMKII beta is sufficient to dock the predominant CaMKII alpha to the actin cytoskeleton. Thus, CaMKII beta functions as a targeting module that localizes a much larger number of CaMKII alpha isozymes to synaptic and cytoskeletal sites of action.