NMDA Receptor 2 (NR2) C-Terminal Control of NR Open Probability Regulates Synaptic Transmission and Plasticity at a Cerebellar Synapse
NMDA Receptor 2 (NR2) C-Terminal Control of NR Open Probability Regulates Synaptic Transmission and Plasticity at a Cerebellar Synapse
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NMDA 受体 2 (NR2) C 端控制 NR 开放概率调节小脑突触的突触传递和可塑性
DOI：
10.1523/jneurosci.22-22-09687.2002
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
E. D’Angelo
中科院分区：
文献类型：
--
作者：
P. Rossi;E. Sola;V. Taglietti;T. Borchardt;F. Steigerwald;J. Utvik;O. Ottersen;G. Köhr;E. D’Angelo
NMDA受体2 （NR2）亚基的c端结构域在突触后密度中调节NMDA受体的定位和功能中起关键作用。然而，这种调节的机制尚不完全清楚。在本文中，我们发现小鼠NR2A和NR2C亚基的c端截断（NR2A/CΔC/ΔC）会损害小脑苔藓纤维-颗粒细胞中继的突触传递和可塑性。通过谷氨酸清除剂谷氨酸丙酮转氨酶和开放通道阻滞剂MK801可以将突触NMDA受体的激活与突触外受体的激活区分开来。NR2A/CΔC/ΔC小鼠表现出突触NMDA受体激活的特异性减少，这是由于通道打开概率降低了几倍，而不是通道电导。免疫检测显示发育正常的NR亚基蛋白表达。NR1抗体的定量免疫金分析表明，受体激活的减少不是由于突触后密度中含有NR1的受体数量的减少。因此，NR2A/NR2C亚基，特别是它们的C末端，通过增加通道打开概率来调节突触NMDA受体的激活和功能，这对于长期增强诱导至关重要。
The C-terminal domain of NMDA receptor 2 (NR2) subunits has been proposed to play a critical role in regulating NMDA receptor localization and function in postsynaptic densities. However, the mechanism of this regulation is not completely understood. In this paper we show that C-terminal truncation of NR2A and NR2C subunits in mice (NR2A/CΔC/ΔC) impairs synaptic transmission and plasticity at the cerebellar mossy fiber–granule cell relay. Activation of synaptic NMDA receptors could be distinguished from that of extrasynaptic receptors by using the glutamate scavenger glutamate pyruvate transaminase and the open channel blocker MK801. NR2A/CΔC/ΔC mice exhibited a specific reduction in synaptic NMDA receptor activation attributable to a severalfold decrease in channel open probability but not channel conductance. Immunodetection revealed normal developmental expression of NR subunit proteins. Quantitative immunogold analyses with an antibody to NR1 indicated that the reduction in receptor activation is not attributed to a reduced number of NR1-containing receptors in postsynaptic densities. Thus, NR2A/NR2C subunits and particularly their C termini regulate synaptic NMDA receptor activation and function by enhancing channel open probability, which is critical for long-term potentiation induction.
大鼠皮质和小脑中 NR1 蛋白选择性剪接的发育差异。
DOI：
10.1016/s0165-3806(00)00079-1
发表时间：
2000
期刊：
Brain research. Developmental brain research
影响因子：
--
作者：
Prybylowski,KL;Wolfe,BB
通讯作者：
Wolfe,BB