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浙江大学学报(医学版)  2021, Vol. 50 Issue (5): 651-658    DOI: 10.3724/zdxbyxb-2021-0167
综述     
GluN3亚基的N-甲基-D-天冬氨酸受体及其在中枢神经系统的功能
孙琦,曹蔚,罗建红()
浙江大学医学院脑科学与脑医学学院,浙江 杭州 310058
The roles of GluN3-containing N-methyl-D-aspartate receptor in central nerve system
SUN Qi,CAO Wei,LUO Jianhong()
School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou 310058, China
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摘要:

中枢神经系统N-甲基-D-天冬氨酸受体(NMDAR)主要由GluN1和GluN2亚基组成,这类经典NMDAR结构和功能已有深入研究。然而,含有GluN3亚基的非经典NMDAR表达量少,没有典型的通道特征,其功能也知之尚少。近年研究发现,GluN3可参与形成两种不同的NMDAR:谷氨酸门控的GluN1/GluN2/GluN3三异聚体NMDAR和甘氨酸门控的GluN1/GluN3二异聚体NMDAR。前者在调节突触成熟时间窗和修剪无用突触方面具有重要作用,成年时表达和活性增高则会导致突触结构和功能的紊乱并与某些神经精神疾病相关;后者表达于内侧僵核并参与负向情绪的调控。本文综述了含GluN3非经典NMDAR的表达、功能特征及其与生理和病理联系的研究进展。

关键词: N-甲基-D-天冬氨酸受体GluN3亚基突触修剪神经发育精神障碍综述    
Abstract:

The N-methyl-D-aspartate receptor (NMDAR) in central nerve system is mostly composed of GluN1 and GluN2 subunits. The classical NMDAR has been intensively studied. However, GluN3?containing NMDAR is much less expressed and have atypical channel properties. Recently, accumulating evidences have revealed two types of GluN3?containing NMDAR: glutamate-gated GluN1/GluN2/GluN3 NMDAR and glycine-gated GluN1/GluN3 NMDAR. The former may play important roles in regulating synapse maturation and pruning non-used synapses, and its elevated expression at the adult stage may alter synaptic reorganization in some neuropsychiatric disorders. The latter is expressed in the medial habenula and involves in control of aversion. This article reviews the recent progresses on the expression, functional properties of GluN3?containing atypical NMDARs and the physiological and pathological relevance.

Key words: N-methyl-D-aspartate receptor    GluN3 subunit    Synaptic pruning    Neural development    Mental disorder    Review
收稿日期: 2021-03-25 出版日期: 2021-12-29
:  R34  
基金资助: 广东省重点领域研发计划(2019B030335001);浙江省自然科学基金(D19H090004)
通讯作者: 罗建红     E-mail: luojianhong@zju.edu.cn
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孙琦,曹蔚,罗建红. 含GluN3亚基的N-甲基-D-天冬氨酸受体及其在中枢神经系统的功能[J]. 浙江大学学报(医学版), 2021, 50(5): 651-658.

SUN Qi,CAO Wei,LUO Jianhong. The roles of GluN3-containing N-methyl-D-aspartate receptor in central nerve system. J Zhejiang Univ (Med Sci), 2021, 50(5): 651-658.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0167        https://www.zjujournals.com/med/CN/Y2021/V50/I5/651

图 1  N-甲基-D-天冬氨酸受体的装配、通道和分布特征A:经典NMDAR通道,由2个GluN1和2个GluN2组成,对钙离子具有高通透性,成簇定位于突触后致密区,静息状态下对镁离子阻滞作用敏感;B:GluN1/GluN2/GluN3三异聚体通道,含1个GluN3A/B亚基,表现出钙离子内流减少,并且对镁离子的电压依赖性阻滞不太敏感;C:GluN1/GluN3二异聚体NMDAR通道,含有2个GluN3A/B亚基,作为相对不透钙离子的兴奋性甘氨酸受体发挥作用,对通道阻滞剂镁离子不敏感. 含GluN3A亚基的NMDAR主要分布在突触外或突触周边. NMDAR:N-甲基-D-天冬氨酸受体.
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