Figure 1 | Translational Psychiatry

Figure 1

From: Frequency of alcohol consumption in humans; the role of metabotropic glutamate receptors and downstream signaling pathways

Figure 1

Simplified schema demonstrating proposed mGluR–eEF2–AMPAR pathway: Postsynaptic binding of glutamate leads to activation of ionotropic (AMPAR, NMDAR shown) and metabatropic (mGlu1/5 shown) glutamate receptors. Activation of mGlu1/5 leads to Gq activation of PLC (not shown) and the mTOR pathway that can affect the activity of Ei4FE and initiation of local RNA translation. Binding of Ca2+/CaM to EEF2K releases eEF2K-Ca/CaM complex from mGlu1/5 and scaffolding protein Homer. EEF2K-CaM phosphorylates EEF2 and switches its activity in global RNA translation to specific RNA translation including CaMK2α and Arc. CaMK2α and Arc interact with AMPARs and with downstream proteins to modulate trafficking of AMPARs in the postsynaptic membrane and regulate synaptic plasticity. AMPAR, α-amino-3-hydroxy-methyl-4-isoxasolepropionic acid receptor; CaMK2α, calcium/calmodulin-dependent protein kinase II alpha; mTOR, mechanistic target of rapamycin.

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