description) Recent evidence from the investigator's laboratory indicates that stimulation of neurotransmitter receptors in an in vitro synaptoneurosome preparation results in the rapid association of mRNAs, including that for the fragile X mental retardation protein (FMRP), with translation complexes at the synapse. Since synaptic activity during development, through its effect on FMRP, may affect structural and functional maturation of the synapse, alterations in FMRP may provide a basis for the alterations seen in fragile X patients. The investigator proposes a series of basic studies of rodent brains designed to explore further 1) the link between receptor-induced phosphorylation cascades and translation events at the synapse; 2) histological evidence for the distribution of other FMR1 family members (FXR1/2); 3) selective effects of different glutamate agonists with respect to phosphorylation of ribosome-associated proteins; 4) evidence for translational control of other mRNAs near the synapse; and 5) synaptic stimulation and protein synthesis in living cells.
| Weiler, Ivan Jeanne; Spangler, Chad C; Klintsova, Anna Y et al. (2004) Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses. Proc Natl Acad Sci U S A 101:17504-9 |
| Angenstein, F; Greenough, W T; Weiler, I J (1998) Metabotropic glutamate receptor-initiated translocation of protein kinase p90rsk to polyribosomes: a possible factor regulating synaptic protein synthesis. Proc Natl Acad Sci U S A 95:15078-83 |
