mGluR1/5 signaling pathways relevant to protein synthesis. Glutamate binding to Gp1 mGluRs activates three main pathways that couple the receptors to translational regulation: (a) the PLC/calcium-calmodulin pathway (orange ovals), (b) the mTOR pathway (blue ovals), and (c) the ERK pathway (green ovals). See main text for details. Key translational regulatory components implicated in these pathways are shown in brown. mGluR1/5 may also inhibit FMRP (red oval) function to regulate translation through a fourth pathway requiring stimulation of PP2A (yellow oval). Question marks indicate undetermined associations. Arrows indicate a positive consequence on downstream components; perpendicular lines indicate an inhibitory consequence. Abbreviations: [Ca2+]i, calcium release from intracellular stores; CaM, calmodulin; ERK, extracellular signal–regulated kinase; FMRP, fragile X mental retardation protein; (Gαq, Gβ, Gγ), heterotrimeric G proteins; InsP3, inositol-1,4,5-triphosphate (InsP3); mGluR, metabotropic glutamate receptor; mTOR, mammalian target of rapamycin; PtdIns, phosphoinositides; PLC, phospholipase C; PP2A, protein phosphatase 2A; Raptor, regulatory-associated protein of mTOR.