Dynamic Control of CaMKII Translocation and Localization in Hippocampal Neurons by NMDA Receptor Stimulation

Calcium-calmodulin–dependent protein kinase II (CaMKII) is thought to increase synaptic strength by phosphorylating postsynaptic density (PSD) ion channels and signaling proteins. It is shown that N -methyl- D -aspartate (NMDA) receptor stimulation reversibly translocates green fluorescent protein–tagged CaMKII from an F-actin–bound to a PSD-bound state. The translocation time was controlled by the ratio of expressed β-CaMKII to α-CaMKII isoforms. Although F-actin dissociation into the cytosol required autophosphorylation of or calcium-calmodulin binding to β-CaMKII, PSD translocation required binding of calcium-calmodulin to either the α- or β-CaMKII subunits. Autophosphorylation of CaMKII indirectly prolongs its PSD localization by increasing the calmodulin-binding affinity.