Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits
Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits
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DOI：
10.1038/nature715
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发表时间：
2002-02-14
期刊：
影响因子：
64.8
通讯作者：
Zhang, DX
中科院分区：
文献类型：
--
作者：
Chatterton, JE;Awobuluyi, M;Zhang, DX
谷氨酸受体的 N-甲基-D-天冬氨酸亚型 (NMDAR) 在中枢神经系统的生理和病理过程中发挥着重要作用，包括神经元发育、可塑性和神经变性(1,2)。由 NR1 和 NR2A-D 亚基 (3,4) 组成的传统异聚 NMDAR 需要双重激动剂（谷氨酸和甘氨酸）才能激活。它们对 Ca2+ 的渗透性也很高，并表现出 Mg2+ 的电压依赖性抑制作用。 NR3A 与 NR1 和 NR2 亚基的共表达可调节 NMDAR 活性(5-7)。在这里，我们报告了 NMDAR 家族最终成员 NR3B 的克隆和表征，该成员与 NR3A 具有高度的序列同源性。根据原位和免疫细胞化学分析，NR3B 主要在运动神经元中表达，而 NR3A 分布更广泛 (5,6)。值得注意的是，当在非洲爪蟾卵母细胞中共表达时，NR3A 或 NR3B 与 NR1 共同组装形成兴奋性甘氨酸受体，该受体不受谷氨酸或 NMDA 的影响，并受到 D-丝氨酸（传统 NMDAR 的共激活剂）的抑制。此外，NR1/NR3A 或-3B 受体形成相对Ca2+ 不可渗透的阳离子通道，对Mg2+、MK-801、美金刚和竞争性拮抗剂具有抗性。在含有 NR3 家族成员的大脑皮质神经元中，甘氨酸会引发爆发性放电，并且膜片表现出可被 D-丝氨酸抑制的甘氨酸反应性单通道。甘氨酸本身通常被认为是一种抑制性神经递质。相反，这些NR1/NR3A或-3B“NMDAR”构成一种兴奋性甘氨酸受体。
The N-methyl-D-aspartate subtype of glutamate receptor (NMDAR) serves critical functions in physiological and pathological processes in the central nervous system, including neuronal development, plasticity and neurodegeneration(1,2). Conventional heteromeric NMDARs composed of NR1 and NR2A-D subunits(3,4) require dual agonists, glutamate and glycine, for activation. They are also highly permeable to Ca2+, and exhibit voltage-dependent inhibition by Mg2+. Coexpression of NR3A with NR1 and NR2 subunits modulates NMDAR activity(5-7). Here we report the cloning and characterization of the final member of the NMDAR family, NR3B, which shares high sequence homology with NR3A. From in situ and immunocytochemical analyses, NR3B is expressed predominantly in motor neurons, whereas NR3A is more widely distributed(5,6). Remarkably, when co-expressed in Xenopus oocytes, NR3A or NR3B co-assembles with NR1 to form excitatory glycine receptors that are unaffected by glutamate or NMDA, and inhibited by D-serine, a co-activator of conventional NMDARs. Moreover, NR1/NR3A or -3B receptors form relatively Ca2+-impermeable cation channels that are resistant to Mg2+, MK-801, memantine and competitive antagonists. In cerebrocortical neurons containing NR3 family members, glycine triggers a burst of firing, and membrane patches manifest glycine-responsive single channels that are suppressible by D-serine. By itself, glycine is normally thought of as an inhibitory neurotransmitter. In contrast, these NR1/NR3A or -3B 'NMDARs' constitute a type of excitatory glycine receptor.