Fig. 1
Endocannabinoid-mediated signaling in the CNS in the normal state. In a normal state with FMR1 protein present, (1) FMRP supports expression of DGKκ and traffics DAGL mRNA, which results in (2) normal production of 2-AG and release into the synaptic cleft, which (3) stimulates presynaptic CB1 receptors resulting in (4) retrograde inhibitory signaling and (5) optimal release of glutamate and activation of mGluR5 receptors and (6) modulation of GABAergic function. 2-AG, 2-arachidonoylglycerol; β-arr, β-arrestin; CB1, cannabinoid type 1 receptor; CNS, central nervous system; DAG, diacylglycerol; DAGL, diacylglycerol lipase; DGKκ, diacylglycerol kinase-κ; FMRP, FMR1 protein; G, G proteins; GABA, γ-aminobutyric acid; mGluR5, group I metabotropic glutamate receptor 5; mRNA, messenger RNA; PA, phosphatidic acid; PIP2, phosphatidylinositol-4,5-bisphosphate; PLC, phospholipase C