Model of the role of the CaM kinase cascade in memory consolidation. At the postsynapse NMDAR activation leads to calcium influx. The incoming calcium binds to calmodulin resulting in the activation of CaMKK. CaMKK activates CaMKI and CaMKIV, when these kinases have bound CaM. Active CaMKI may induce local translation of dendritic mRNA. Active CaMKIV phosphorylates CREB and CREB-binding protein (CBP) in the nucleus to induce gene transcription, which ultimately results in protein synthesis. The newly synthesized proteins are targeted to the activated synapses; they are essential for memory consolidation. Red arrows indicate phosphorylations and dashed arrows illustrate translocation of the protein.
