Rapid synaptic remodeling by protein kinase C: reciprocal translocation of NMDA receptors and calcium/calmodulin-dependent kinase II.

In contrast to the rapid regulation of AMPA receptors, previous evidence has supported the idea that the synaptic density of NMDA-type glutamate receptors is fairly static, modulated only over a long time scale in a homeostatic manner. We report here that selective activation of protein kinase C (PKC) with phorbol esters induces a rapid dispersal of NMDA receptors from synaptic to extrasynaptic plasma membrane in cultured rat hippocampal neurons. PKC activation induced a simultaneous translocation of calcium/calmodulin-dependent kinase II (CaMKII) to synapses but no change in spine number, presynaptic terminal number, or the distribution of AMPA receptors or the synaptic scaffolding protein PSD-95. PKC-induced accumulation of CaMKII was dependent on filamentous actin, whereas dispersal of NMDA receptors occurred by a different mechanism independent of actin or CaMKII. Consistent with the decrease in synaptic density of NMDA receptors, phorbol ester pretreatment reduced excitotoxicity. These results reveal a surprisingly dynamic nature to the molecular composition and functional properties of glutamatergic postsynaptic specializations.