Cloning and characterization of a novel NMDA receptor subunit NR3B: a dominant subunit that reduces calcium permeability
Cloning and characterization of a novel NMDA receptor subunit NR3B: a dominant subunit that reduces calcium permeability
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DOI：
10.1016/s0169-328x(02)00173-0
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发表时间：
2002-04-30
期刊：
影响因子：
--
通讯作者：
Yuzaki, M
中科院分区：
文献类型：
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作者：
Matsuda, K;Kamiya, Y;Yuzaki, M
我们报道了一种新的NMDA受体亚基cDNA的克隆和表征，该亚基编码1003个氨基酸的预测多肽。系统发育分析表明，该亚基与NR3A亲缘关系最为密切。因此我们称它为NR3B。谷氨酸受体的重要功能域；如配体结合域、通道孔和通道门等，在NR3B中是保守的。NR3B mRNA在脑桥、中脑、髓质和脊髓中高表达，而在前脑和小脑中低表达。尽管NR3A mRNA的表达在出生第二周后急剧下降，但NR3B mRNA在全脑的表达水平在出生后发育和成年期间是恒定的。共免疫沉淀分析显示，NR3B可与NR1a和NR2A亚基在异源细胞中形成NMDA受体复合物。虽然NR3B单独表达不能重建功能性NMDA受体，但在表达NR1a和NR2A的细胞中，NR3B的共表达降低了谷氨酸诱导电流的Ca2+通透性。这些结果表明NR3B是一个主要的调节亚基，可以改变NMDA受体的功能。由于NMDA受体的hi，h Ca2+通透性被认为是NMDA受体在神经发育，突触可塑性和神经元死亡中发挥关键作用的关键特征，NR3B可能有助于调节这些生理和病理过程。(C) 2002 Elsevier Science B.V.版权所有
We report the cloning and characterization of a novel NMDA receptor subunit cDNA, which encodes a predicted polypeptide of 1003 amino acids. Phylogenic analysis indicates that this new subunit is most closely related to NR3A. Therefore, we term it NR3B. Important functional domains of glutamate receptor,.;, such as the ligand-binding domain, the channel pore, and the channel gate, are conserved in NR3B. NR3B mRNA was expressed highly in pons, midbrain, medulla, and the spinal cord, but at low levels in the forebrain and the cerebellum. Although NR3A mRNA expression decreases sharply after the second postnatal weeks, NR3B mRNA expression levels in whole brain were constant during postnatal development and into adult. Coimmunoprecipitation analysis showed that NR3B could form NMDA receptor complex with NR1a and NR2A subunits in heterologous cells. Although expression of NR3B alone did not reconstitute functional NMDA receptors, coexpression of NR3B reduced the Ca2+ permeability of glutamate-induced currents in cells expressing NR1a and NR2A. These results indicate that NR3B is a dominant modulatory subunit that can modify the function of NMDA receptors. Since hi,h Ca2+ permeability of NMDA receptors is thought to be a key feature for NMDA receptors to play critical roles in neurodevelopment, synaptic plasticity, and neuronal death, NR3B may contribute to the regulation of these physiological and pathological processes. (C) 2002 Elsevier Science B.V. All rights reserved.