Diversity in NMDA receptor composition: many regulators, many consequences.
Diversity in NMDA receptor composition: many regulators, many consequences.
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DOI：
10.1177/1073858411435129
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发表时间：
2013-02
期刊：
影响因子：
--
通讯作者：
Roche KW
中科院分区：
文献类型：
--
作者：
Sanz-Clemente A;Nicoll RA;Roche KW
N-甲基-D-天冬氨酸受体（NMDARs）是离子型谷氨酸受体的一种亚型，在学习、记忆和突触发育中发挥重要作用。NMDAR组装为由两个GluN 1亚基和两个GluN 2或GluN 3亚基组成的四聚体。虽然NMDAR在整个中枢神经系统中广泛表达，但它们的数量、定位和亚基组成受到严格调控，并且以细胞和突触特异性方式存在差异。脑面积、发育阶段和突触活动水平是调节NMDAR的一些因素。控制亚基特异性NMDAR功能的分子机制包括亚基转录/翻译的发育调节、通过分泌途径的差异运输、转录后修饰如磷酸化和蛋白质-蛋白质相互作用。GluN 2A和GluN 2B亚基在皮质和海马中高度表达，并赋予内源性NMDAR许多独特的性质。重要的是，突触NMDAR亚基组成在突触成熟期间以及响应于活动和经历而从主要含GluN 2B的NMDAR改变为含GluN 2A的NMDAR。最近已经确定了这种GluN 2亚基开关的一些分子机制。此外，突触和突触外NMDAR之间的平衡在几种神经元疾病中被改变。本文就NMDAR亚基特异性调控机制的研究进展作一综述。
N-methyl-D-aspartate receptors (NMDARs) are a subtype of ionotropic glutamate receptor, which play a central role in learning, memory, and synaptic development. NMDARs are assembled as tetramers composed of two GluN1 subunits and two GluN2 or GluN3 subunits. Although NMDARs are widely expressed throughout the central nervous system, their number, localization, and subunit composition are strictly regulated and differ in a cell- and synapse-specific manner. The brain area, developmental stage and level of synaptic activity are some of the factors that regulate NMDARs. Molecular mechanisms that control subunit-specific NMDAR function include developmental regulation of subunit transcription/translation, differential trafficking through the secretory pathway, post-transcriptional modifications such as phosphorylation, and protein-protein interactions. The GluN2A and GluN2B subunits are highly expressed in cortex and hippocampus and confer many of the distinct properties on endogenous NMDARs. Importantly, the synaptic NMDAR subunit composition changes from predominantly GluN2B-containing to GluN2A-containing NMDARs during synaptic maturation and in response to activity and experience. Some of the molecular mechanisms underlying this GluN2 subunit switch have been recently identified. In addition, the balance between synaptic and extrasynaptic NMDARs is altered in several neuronal disorders. Here, we summarize the recent advances in the identification of NMDAR subunit-specific regulatory mechanisms.
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影响因子：
16.2
作者：
Gray JA;Shi Y;Usui H;During MJ;Sakimura K;Nicoll RA
通讯作者：
Nicoll RA
DOI：
10.1523/jneurosci.1034-10.2011
发表时间：
2011-01-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chen BS;Thomas EV;Sanz-Clemente A;Roche KW
通讯作者：
Roche KW
DOI：
10.1073/pnas.0811025106
发表时间：
2008-12-30
影响因子：
11.1
作者：
Elias, G. M.;Elias, L. A. B.;Nicoll, R. A.
通讯作者：
Nicoll, R. A.
影响因子：
16.2
作者：
Borgland, SL;Taha, SA;Bonci, A
通讯作者：
Bonci, A
影响因子：
64.5
作者：
Dalva, MB;Takasu, MA;Greenberg, ME
通讯作者：
Greenberg, ME