|Molecular Mechanisms of Cytoskeletal Regulation by FMRP
Samie Jaffrey, 2/1/2005
One feature of neurons that display abnormalities in FMR1 is that
dendritic spines have abnormal shapes. This suggests that FMR1 has a
role in controlling the shapes of these spines. Since spines are key structures involved in
learning, memory, and behavior, the abnormal structure of these spines may explain some of
the features seen in patients with Fragile X. What is unclear is how FMR1, which is known
to regulate mRNA translation, controls the underlying cytoskeleton of dendritic spines.
We are investigating how FMR1 regulates an mRNA that encodes a critical regulator of
the neuronal cytoskeleton called RhoA. RhoA has independently been shown to affect dendritic structure
and its mRNA has been shown to interact with FMR1, thus suggesting an appealing connection between FMR1,
RhoA, and spine abnormalities. If spine abnormalities are due to the inability of FMR1 to regulate RhoA,
pharmacotherapy directed against RhoA or the RhoA molecular pathway
may be suitable for reversing the symptoms of Fragile X.