Fig. 1

Opponent regulation of protein synthesis by FMRP and GpI mGluRs. FMRP is a negative regulator of translation at the synapse. Stimulation of GpI mGluRs with DHPG leads to the synthesis of proteins. Furthermore, many of the long-term consequences of Gp1 mGluR activation are protein synthesis dependent. The mGluR theory posits that in the absence of FMRP, as is the case in Fragile X syndrome, this balance between FMRP and Gp1 mGluRs is lost, and unchecked protein synthesis at the synapse leads to the characteristic features of the disease. Furthermore, this balance could be restored by reducing Gp1 mGluR activity at the synapse, by either knockdown or pharmacological blockade of the receptor. The therapeutic implication of the theory is that symptoms of FXS syndrome could be corrected by appropriate modulation of GpI mGluR signaling