Through a focus on neural protein synthesis, the William T. Greenough Laboratory (BI) is reaching some startling conclusions about nervous system development. Current Greenough lab research into the protein FMRP has important implications for understanding Fragile X Mental Retardation Syndrome, the most common genetically inherited form of mental retardation, as well as FMRP's role in protein synthesis. A paper by Greenough Lab member Ivan Jeanne Weiler, Professor Greenough, et al., published by the Proceedings of the National Academy of Sciences discusses recent findings of their research.
The paper, 'Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses' states: "Fragile X mental retardation is caused by absence of the RNA-binding protein FMRP, encoded by the FMR1 gene." Weiler, adjunct Professor of Psychology, said there is also evidence that FMRP may play a larger role in dendritic protein synthesis that what was previously thought, such as in transport and/or translation of mRNA in dendrites.
"What we think now is the reason FMRP, this one single protein, has so many and such varying effects is because it is kind of a master protein which regulates a whole group, maybe 80, maybe 200 other proteins," Weiler said.
Fragile X mental retardation occurs when FMRP is absent. The lab's research into FMRP is important for confirming a biochemical basis for a deficient protein synthesis in response to stimulation at synapses in those afflicted with the syndrome. Their research demonstrated that a deficiency in FMRP leads to an inability to regulate the rapid production of other proteins needed to respond to changing surroundings and make the new neuron connections called synapses that are required for normal development.
"What we reported in this paper was the Fragile X mice do not have this rapid protein synthesis response," Weiler said. "The concept now that our lab has developed is that all of our brains have an overproduction of synapses. The connections that are not useful are retracted, the ones that are useful are retained and strengthened."
For those with Fragile X syndrome, both wanted and unwanted synapses are not retracted, leading to a "noisy environment" in their brains. For more on their important findings involving the studies of brain development and mental retardation, read the full text of the paper by clicking on the title above.