Mechanisms underlying NMDA receptor localization

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DESCRIPTION (provided by applicant): Synapse formation during development is an important step in the establishment of the mammalian brain. Trafficking of proteins and receptors to and from the synapse helps to maintain homeostasis. Diseases such as Alzheimer's and Rett Syndrome occur when this homeostasis is disrupted. One particular receptor, the NMDA receptor, is important for proper functioning of the synapse. My preliminary studies suggest that snapin forms a complex with the NMDA receptor subunit NR1 and decreases the number of NR1 clusters per unit area of dendrite in hippocampal neurons. Therefore, it is important to understand how this interaction occurs and how it affects functional NMDA receptor trafficking. Our first set of experiments will determine which portion of snapin interacts with NR1 and which splice variant of NR1 interacts with snapin. The second group of experiments will determine how snapin affects functional NMDA receptor clustering and synaptic localization. The third set of experiments will determine if snapin affects cell surface expression of functional NMDA receptors. Taken together, the results from these experiments will give insight into NMDA receptor trafficking.