Fragile X syndrome, a leading cause of autism and the most common form of inherited intellectual disability, results from the loss of Fragile X mental retardation protein (FMRP). FMRP is an RNA binding protein with a well-elucidated post-synaptic role in regulation of synaptic plasticity. Emerging evidence also indicates an axonal and presynaptic role for FMRP. Work from our laboratory has identified FMRP as a component of an axonal and presynaptic granule, termed the Fragile X granule (FXG), which also contains its autosomal homologs Fragile X related protein 2 (FXR2P) and Fragile X related protein 1 (FXR1P). The axonal localization of FMRP raises several questions such as: What axonal messages are associated with FMRP? How does FMRP regulate the expression of these messages and proteins? This thesis seeks to address the role of FMRP in regulating axonal mRNAs in vivo. I have focused on the circuit between olfactory sensory neurons (OSNs) and the olfactory bulb. Within this system, the message for olfactory marker protein (OMP) is localized to OSN axons, where it co-localizes with a subset of FXGs. I have addressed the role of FMRP in regulating axonal olfactory marker protein (OMP). OMP message localizes with a subset of FXGs in the olfactory bulb. I found that FMRP regulates the protein expression of OMP in the axonal domain of OSNs. Interestingly, FMRP does not appear to be required for the localization of OMP mRNA to axons, suggesting that it is not actively involved in the trafficking of this message. This work provides in vivo evidence for FMRP's regulation of an axonal message.<br/><br/>
Berk-Rauch, Hanna E.,
"FMRP Regulates the Expression of Axonal Messages In Vivo"
Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations.
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