Model of the role of ERK1/2 signaling in memory consolidation. At the postsynapse NMDAR activation leads to calcium influx. There are two routes to activate the MAPK cascade. First, incoming calcium binds to calmodulin resulting in the activation of adenylate cyclase 1 and 8 leading to activation of the exchange protein activated by cAMP-(EPAC) that activates the small GTPase Rap1 (GTP-bound form is active) (Yang et al. 2012), which binds to, and thereby activates, Raf kinase inducing the MAPK cascade. Second, CaM induces the Ras nucleotide exchange factors RasGRF1 and 2 leading to Ras activation (GTP bound), which binds to, and thereby activates, Raf kinase inducing the MAPK cascade. Activated ERK1/2 regulate local translation of dendritic mRNA. They also contribute to the induction of transcription of plasticity-related genes by activation of the transcription factors CREB and ELK-1. 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.
