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 CaMKIIα and CaMKIIβ isoforms are not yet known. Here, we use green fluorescent protein–tagged (GFP-tagged) CaMKII isoforms and show that CaMKIIβ is bound to F-actin in dendritic spines and cell cortex while CaMKIIα is largely a cytosolic enzyme. When expressed together, the two isoforms form large heterooligomers, and a small fraction of CaMKIIβ is sufficient to dock the predominant CaMKIIα to the actin cytoskeleton. Thus, CaMKIIβ functions as a targeting module that localizes a much larger number of CaMKIIα isozymes to synaptic and cytoskeletal sites of action.
