With a $35,000 in grant from FRAXA Research Foundation, Dr. Justin Fallon and his team at Brown University studied systematic mapping of Fragile X granules in developing mouse brains, revealing a potential role for presynaptic FMRP in sensorimotor functions.
Sandra Won, PhD
FRAXA Postdoctoral Fellow (2001)
by Justin Fallon, 7/1/2001
Fragile X syndrome is caused by the absence of the FMR1 gene’s protein product, FMRP. However, little is known about the normal function and regulation of FMRP or how its loss leads to cognitive impairment. We do know that the translation of RNAs into proteins at synapses (the junctions between nerve cells) is essential for learning and memory. A growing body of evidence suggests a role for FMRP in RNA binding, transport, and/or translation. Intriguingly, FMR1 messenger RNA is present at the synapses and its translation can be stimulated by neurotransmitters. The close relationship between FMRP protein and message and RNA metabolism at synapses provides a pathway to link FMRP function at the molecular level to its role in higher functions in the brain. Therefore, an understanding of the translational regulation of FMRP is necessary for understanding the molecular mechanisms leading to Fragile X.
We are investigating the molecular mechanisms of activity-induced Fragile X protein synthesis using a combined molecular, cellular and biochemical approach in cultured neurons and in mice. Of special interest is the potential role of a particular process, recently identified in our laboratory, by which synaptic mRNAs are translated into proteins. The mRNAs encoding FMRP and a related protein, FXR2P, contain unique tags indicating that they may be regulated by this process. The overall goal of our studies is to understand the role FMRP plays in translating other proteins and thereby strengthening and/or weakening synapses and, ultimately, enabling learning and memory. Such information could contribute to designing strategies and treatments for overcoming the loss of FMRP in Fragile X syndrome.