Driving AMPA receptors into synapses by LTP and CaMKII: Requirement for GluR1 and PDZ domain interaction

To elucidate mechanisms that control and execute activity-dependent synapti c plasticity, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate recepto rs (AMPA-Rs) with an electrophysiological tag were expressed in rat hippoca mpal neurons. Long-term potentiation (LTP) or increased activity of the cal cium/calmodulin-dependent protein kinase II (CaMKII) induced delivery of ta gged AMPA-Rs into synapses. This effect was not diminished by mutating the CaMKII phosphorylation site on the GLuR1 AMPA-R subunit, but was blocked by mutating a predicted PDZ domain interaction site. These results show that LTP and CaMKII activity drive AMPA-Rs to synapses by a mechanism that requi res the association between GluR1 and a PDZ domain protein.