The responsiveness of a neuron to neurotransmitter released from a presynaptic cell is determined by the type and amount of receptor expressed on the postsynaptic membrane. The unique distribution of receptors and their subtypes within a single cell and throughout the brain requires highly selective intracellular targeting mechanisms. My laboratory studies the regulation of glutamate receptor trafficking and localization using a combination of biochemical and molecular techniques. In the past year, we have investigated the differential sorting of NMDA receptor subunits following endocytosis from the plasma membrane. Using both heterologous cells and primary hippocampal cultures, we examined the fate of internalized receptors. The NR2B subunit, which is highly expressed early in development, is sorted into recycling endosomes; whereas the NR2A subunit, which is highly expressed in adult animals, is sorted into the late endosomal/lysosomal pathway. Our initial findings support unique contributions of the individual NMDA receptor subunits to NMDA receptor stabilization at the cell surface and their ability to recycle from endocytic compartments back to the cell surface. In a separate project, we have investigated the phosphorylation of the metabotropic glutamate receptor mGluR5 by a variety of protein kinases in vitro. We are identifying the specific residues that are phosphorylated, and we will soon begin comparing these results to the phosphorylation of mGluR5 in primary neuronal cultures. These studies will allow us to study the functional consequences of glutamate receptor phosphorylation and the regulation of receptor trafficking and localization.
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