Grant: Operating Grant - PA: Genetics (Bridge Funding: Research Priorities)

The formation and storage of memories relies on the production of new proteins, which can occur locally at points of connection (synapses) between neurons in the brain. These new proteins support long-lasting changes in the strength and size of synapses. To ensure that proteins are made at the appropriate time and location to enable these changes to occur, messenger RNA (mRNA) translation is tightly controlled by RNA-binding proteins. Fragile X Related Protein 1 (FXR1P) is an RNA-binding protein with high homology to Fragile X Mental Retardation Protein (FMRP) and is known to regulate mRNA translation in non-neuronal cells. However, unlike FMRP, very little is known about the role of FXR1P in the central nervous system. We recently discovered that FXR1P is highly produced by neurons in the brain and co-localized with protein synthesis machinery and mRNAs at synapses. Genetically removing FXR1P from select neuron populations in the brain results in important molecular, physiological, and behavioral changes in mice. Ultimately, FXR1P functions as a key molecular brake in the brain that controls the strengthening of synapses which is important for memory formation. In this grant we will: 1) Investigate the properties of FXR1P at synapses, 2) characterize its molecular interactions, and 3) uncover how it participates in brain diseases including Alzheimer's disease.