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 defe ct in the protein (FMRP) encoded by the FMR1 gene. FMRP is found in dendrit es and synapses as well as in the neuronal cell soma and nucleus, and altho ugh it is known to bind to RNA, the function of the protein in neurons is n ot known. We have studied activity-dependent changes in postsynaptically lo calized 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 knoc kout 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 deve lopment results in structural and functional maturation of the synapse. We hypothesize that synaptic synthesis of FMRP may be essential for activity-b ased synapse maturation and elimination, a key process in normal brain deve lopment. (C) 1999 Wiley-Liss, Inc.