FIGURE 5.

Model, illustrating the regulation of FMRP-mediated translation of Syngap1 during development. This model shows that FMRP regulates Syngap1 mRNA translation, which in turn regulates NMDAR-mediated signaling. In WT, NMDAR stimulation in synapse led to increased phosphorylation of eEF2, which resulted in global translation inhibition and the signaling was efficiently regulated by SYNGAP1. Whereas, in Syngap1^-/+ at PND14-16, NMDAR-mediated signaling was impaired as depicted by the loss of phosphorylation response to eEF2 due to a decreased level of SYNGAP1. At PND21-23 in Syngap1^-/+, FMRP level was low that increased translation of Syngap1 mRNA leading to an increased SYNGAP1 level compared to PND14-16. Thus, an elevated level of SYNGAP1 might recover the NMDAR-mediated signaling via phosphorylation of eEF2.