Model of the role of CaMKII in synaptic potentiation underlying memory formation. At the postsynapse NMDA receptor (NMDAR) activation leads to calcium influx. The incoming calcium binds to calmodulin (CaM) resulting in the activation of CaMKII, consisting of αCaMKII (red) and βCaMKII subunits (orange). Inactive CaMKII is bound to F-actin via binding of βCaMKII subunits, whereas active CaMKII dissociates from F-actin. Activation of CaMKII also leads to an intersubunit autophosphorylation of αCaMKII at threonine-286 to prolong its kinase activity (phosphorylation is shown as a white “P”). Activated CaMKII phosphorylates the stargazin subunit of AMPA receptor (AMPAR) complexes enabling AMPARs to translocate to the postsynaptic density (PSD). This increases the number of AMPARs in the PSD causing an increase in synaptic transmission. Further, activated CaMKII translocates to the PSD and binds to the NMDAR via αCaMKII subunits, where CaMKII can phosphorylate GluA1 subunits of the AMPAR to enhance the conductivity of these receptors. Additionally, αCaMKII mRNA is locally translated in dendrites and newly synthesized αCaMKII is thought to translocate into the dendritic spine. This local translation is required for LTM, but not STM. Red arrows indicate phosphorylations and dashed arrows illustrate protein translocation. The model is a modification of the one presented in Lisman et al. 2012.
