FRAGILE-X MENTAL-RETARDATION PROTEIN IS TRANSLATED NEAR SYNAPSES IN RESPONSE TO NEUROTRANSMITTER ACTIVATION

Local translation of proteins in distal dendrites is thought to suppor t synaptic structural plasticity. We have previously shown that metabo tropic glutamate receptor (mGluR1) stimulation initiates a phosphoryla tion cascade, triggering rapid association of some mRNAs with translat ion machinery near synapses, and leading to protein synthesis, To dete rmine the identity of these mRNAs, a cDNA library produced from distal nerve processes was used to screen synaptic polyribosome-associated m RNA, We identified mRNA for the fragile X mental retardation protein ( FMRP) in these processes by use of synaptic subcellular fractions, ter med synaptoneurosomes. We found that this mRNA associates with transla tional complexes in synaptoneurosomes within 1-2 min after mGluR1 stim ulation of this preparation, and we observed increased expression of F MRP after mGluR1 stimulation, In addition, we found that FMRP is assoc iated with polyribosomal complexes in these fractions, in vivo, we obs erved FMRP immunoreactivity in spines, dendrites, and somata of the de veloping rat brain, but not in nuclei or axons, We suggest that rapid production of FMRP near synapses in response to activation may be impo rtant for normal maturation of synaptic connections.