Mechanisms of CaMKII action in long-term potentiation

The mechanisms that result in synapse-specific activation of calcium/calmodulin-dependent protein kinase II (CaMKII) have been determined.CaMKII translocates to the synapse during long-term potentiation (LTP), in part owing to binding of CaMKII to the NMDA-type glutamate receptor (NMDAR).One component of early LTP involves CaMKII phosphorylation of the AMPA-type glutamate receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which increases the average channel conductance of AMPARs.Early LTP also involves the phosphorylation of stargazin by CaMKII, which allows extrasynaptic AMPARs to bind to postsynaptic density protein 95 (PSD95), thereby anchoring more AMPARs at the synapse.The molecular memory at a synapse may involve the formation of CaMKII–NMDAR complexes.Late LTP involves spine and synapse growth, the underlying mechanisms of which are not known.