Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor
Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor
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DOI：
10.1016/s0092-8674(02)00962-5
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发表时间：
2002-10-18
期刊：
影响因子：
64.5
通讯作者：
Liu, F
中科院分区：
文献类型：
--
作者：
Lee, FJS;Xue, S;Liu, F
多巴胺D1样受体，由D1和D5受体组成，已被证明可调节谷氨酸介导的快速兴奋性突触神经传递。在这里，我们报告说，多巴胺D1受体调节NMDA谷氨酸受体介导的功能，通过直接的蛋白质-蛋白质相互作用。D1受体羧基尾的两个区域可直接选择性地与NMDA谷氨酸受体亚基NR 1 -1a和NR 2A偶联。虽然一种相互作用涉及抑制NMDA受体门控电流，但另一种相互作用涉及通过PI-3激酶依赖性途径减弱NMDA受体介导的兴奋性毒性。
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.