Synaptic synthesis of the Fragile X protein: possible involvement in synapse maturation and elimination.

Fragile X mental retardation syndrome results from the absence of or a defect in the protein (FMRP) encoded by the FMR1 gene. FMRP is found in dendrites and synapses as well as in the neuronal cell soma and nucleus, and although it is known to bind to RNA, the function of the protein in neurons is not known. We have studied activity-dependent changes in postsynaptically localized protein translation in central nervous system neurons. We find that FMRP is one of the proteins produced at synapses following stimulation of metabotropic glutamate receptors. We have also observed that Fragile X knockout mice, like human Fragile X patients, have excess numbers of long, thin, immature-appearing dendritic processes. Together, these findings suggest that FMRP plays a role in the process whereby synaptic activity during development results in structural and functional maturation of the synapse. We hypothesize that synaptic synthesis of FMRP may be essential for activity-based synapse maturation and elimination, a key process in normal brain development.