Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor |
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Authors: | Lee Frank J S Xue Sheng Pei Lin Vukusic Brian Chéry Nadege Wang Yushan Wang Yu Tian Niznik Hyman B Yu Xian-min Liu Fang |
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Institution: | Department of Neuroscience, Centre for Addiction and Mental Health, Clarke Division, University of Toronto, Toronto, M5T 1R8, Ontario, Canada |
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Abstract: | Dopamine D1-like receptors, composed of D1 and D5 receptors, have been documented to modulate glutamate-mediated fast excitatory synaptic neurotransmission. Here, we report that dopamine D1 receptors modulate NMDA glutamate receptor-mediated functions through direct protein-protein interactions. Two regions in the D1 receptor carboxyl tail can directly and selectively couple to NMDA glutamate receptor subunits NR1-1a and NR2A. While one interaction is involved in the inhibition of NMDA receptor-gated currents, the other is implicated in the attenuation of NMDA receptor-mediated excitotoxicity through a PI-3 kinase-dependent pathway. |
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