Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor.
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.
Lee
Frank J S
FJ
Department of Neuroscience, Centre for Addiction and Mental Health, Clarke Division, University of Toronto, Toronto, M5T 1R8, Ontario, Canada
Xue
Sheng
S
Pei
Lin
L
Vukusic
Brian
B
Chéry
Nadege
N
Wang
Yushan
Y
Wang
Yu Tian
YT
Niznik
Hyman B
HB
Yu
Xian-min
XM
Liu
Fang
F
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001552:Benzazepines / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D008956:Models, Chemical; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D000077191:Wortmannin
D000730:Androstadienes; D001552:Benzazepines; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D000077191:Wortmannin; C409466:NR1 NMDA receptor; C067113:SK&F 81297