Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system, and in addition to its central role in fast excitatory signaling it is also involved in synaptogenesis, synaptic plasticity, and the pathogenesis of certain neurologic diseases. Although glutamate acts as a neurotransmitter in all pathways of the central nervous system, the response to glutamate is not uniform at all glutamatergic synapses and varies with the type of glutamate receptor expressed on the postsynaptic membrane. In this context, we are interested in studying synapse-specific expression of postsynaptic NMDA and metabotropic glutamate receptors. My laboratory characterizes the molecular mechanisms underlying neurotransmitter receptor transport and localization at the synapse using several research strategies which include (1) defining sorting motifs present in neurotransmitter receptor cytosolic domains, (2) isolating neurotransmitter receptor-associated proteins, and (3) determining the role of protein-protein interactions in trafficking and specific synapse localization. Using these cell biological approaches, we hope to elucidate the mechanisms of neurotransmitter receptor trafficking in neurons and the role of accessory proteins at central synapses.
- Mota Vieira M, Nguyen TA, Wu K, Badger JD 2nd, Collins BM, Anggono V, Lu W, Roche KW. An Epilepsy-Associated GRIN2A Rare Variant Disrupts CaMKIIα Phosphorylation of GluN2A and NMDA Receptor Trafficking. Cell Rep. 2020;32(9):108104.
- Nguyen TA, Wu K, Pandey S, Lehr AW, Li Y, Bemben MA, Badger JD 2nd, Lauzon JL, Wang T, Zaghloul KA, Thurm A, Jain M, Lu W, Roche KW. A Cluster of Autism-Associated Variants on X-Linked NLGN4X Functionally Resemble NLGN4Y. Neuron. 2020;106(5):759-768.e7.
- Paskus JD, Tian C, Fingleton E, Shen C, Chen X, Li Y, Myers SA, Badger JD 2nd, Bemben MA, Herring BE, Roche KW. Synaptic Kalirin-7 and Trio Interactomes Reveal a GEF Protein-Dependent Neuroligin-1 Mechanism of Action. Cell Rep. 2019;29(10):2944-2952.e5.
- Bemben MA, Nguyen TA, Li Y, Wang T, Nicoll RA, Roche KW. Isoform-specific cleavage of neuroligin-3 reduces synapse strength. Mol Psychiatry. 2019;24(1):145-160.
- Liu S, Zhou L, Yuan H, Vieira M, Sanz-Clemente A, Badger JD 2nd, Lu W, Traynelis SF, Roche KW. A Rare Variant Identified Within the GluN2B C-Terminus in a Patient with Autism Affects NMDA Receptor Surface Expression and Spine Density. J Neurosci. 2017;37(15):4093-4102.
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