Regulation of the NMDA receptor by its cytoplasmic domains: (How) is the tail wagging the dog?
Regulation of the NMDA receptor by its cytoplasmic domains: (How) is the tail wagging the dog?
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DOI：
10.1016/j.neuropharm.2021.108634
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发表时间：
2021-09-01
影响因子：
4.7
通讯作者：
Koleske AJ
中科院分区：
文献类型：
--
作者：
Ishchenko Y;Carrizales MG;Koleske AJ
由N-甲基-D-天冬氨酸受体（NMDAR）介导的兴奋性神经传递对于脑中突触发育、功能和可塑性至关重要。NMDAR是介导突触传递和可塑性的四聚体阳离子通道。广泛的人类研究表明，NMDAR亚基基因（GRIN基因）中存在遗传变异，这些变异与神经发育和神经精神疾病相关，包括自闭症谱系障碍（ASD）、癫痫（EP）、智力残疾（ID）、注意缺陷多动障碍（ADHD）和精神分裂症（SCZ）。NMDAR亚基具有独特的模块化结构，具有四个半自治域。在这里，我们专注于羧基末端结构域（CTD），也被称为细胞内的C-尾，它的长度在谷氨酸受体亚基之间变化，是氨基酸序列方面最多样化的结构域。CTD显示与任何已知蛋白没有序列同源性，但编码用于细胞内结合蛋白和共价修饰的短对接基序。本文就CTD在NMDA膜调节、突触靶向、稳定、降解靶向、变构调节和代谢信号转导等方面的重要作用进行综述。
Excitatory neurotransmission mediated by N-methyl-D-aspartate receptors (NMDARs) is critical for synapse development, function, and plasticity in the brain. NMDARs are tetra-heteromeric cation-channels that mediate synaptic transmission and plasticity. Extensive human studies show the existence of genetic variants in NMDAR subunits genes (GRIN genes) that are associated with neurodevelopmental and neuropsychiatric disorders, including autism spectrum disorders (ASD), epilepsy (EP), intellectual disability (ID), attention deficit hyperactivity disorder (ADHD), and schizophrenia (SCZ). NMDAR subunits have a unique modular architecture with four semiautonomous domains. Here we focus on the carboxyl terminal domain (CTD), also known as the intracellular C-tail, which varies in length among the glutamate receptor subunits and is the most diverse domain in terms of amino acid sequence. The CTD shows no sequence homology to any known proteins but encodes short docking motifs for intracellular binding proteins and covalent modifications. Our review will discuss the many important functions of the CTD in regulating NMDA membrane and synaptic targeting, stabilization, degradation targeting, allosteric modulation and metabotropic signaling of the receptor.
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影响因子：
4.6
作者：
Addis L;Virdee JK;Vidler LR;Collier DA;Pal DK;Ursu D
通讯作者：
Ursu D
影响因子：
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作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.1517045112
发表时间：
2015-12-15
影响因子：
11.1
作者：
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通讯作者：
Reese, Thomas S.
影响因子：
5.3
作者：
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