TRANSLOCATION OF AUTOPHOSPHORYLATED CALCIUM CALMODULIN-DEPENDENT PROTEIN-KINASE-II TO THE POSTSYNAPTIC DENSITY/

Calcium/calmodulin-dependent protein kinase II (CaMKII) undergoes calc ium-dependent autophosphorylation, generating a calcium-independent fo rm that may serve as a molecular substrate for memory. Here we show th at calcium-independent CaMKII specifically binds to isolated postsynap tic densities (PSDs), leading to enhanced phosphorylation of many PSD proteins including the pha-amino-3-hydroxy-5-methyl-4-isoxazole-propio nic acid (AMPA)-type glutamate receptor. Furthermore, binding to PSDs changes CaMKII hom a substrate for protein phosphatase 2A to a protein phosphatase I substrate. Translocation of CaMKII to PSDs occurs in hi ppocampal slices following treatments that induce CaMKII autophosphory lation and a form of long term potentiation. Thus, synaptic activation leads to accumulation of autophosphorylated, activated CaMKII in the PSD. This increases substrate phosphorylation and affects regulation o f the kinase by protein phosphatases, which may contribute to enhancem ent of synaptic strength.