Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins
Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins
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DOI：
10.1073/pnas.1002690107
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发表时间：
2010-11-09
影响因子：
11.1
通讯作者：
Groc, Laurent
中科院分区：
文献类型：
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作者：
Bard, Lucie;Sainlos, Matthieu;Groc, Laurent
NMDA受体中NR2亚基的相对含量赋予突触特定的信号特性和可塑性。然而，动态调控突触NMDAR的机制，特别是2A-NMDAR，仍然知之甚少。在这里，我们利用高分辨率成像在单分子水平上研究了NR2 C末端与含有PSD-95/Discs-Large/ZO-1同源(PDZ)支架蛋白的蛋白质之间的动态相互作用。我们报道了一个仿生的二价竞争配体，模拟NR2AC端的最后15个氨基酸，在几分钟的时间尺度上特异性地有效地破坏了2A-NMDAR之间的相互作用，而不是2B-NMDARs和PDZ蛋白之间的相互作用。此外，将2A-NMDAR移出突触会导致突触NR2B-NMDAR的代偿性增加，这为2A-或2B-NMDAR的锚定机制不同提供了功能证据。这些数据揭示了NR2亚单位二价排列在突触内提供特定锚定方面的意想不到的作用，突显了在自然条件下研究这种动态相互作用的必要性。
The relative content of NR2 subunits in the NMDA receptor confers specific signaling properties and plasticity to synapses. However, the mechanisms that dynamically govern the retention of synaptic NMDARs, in particular 2A-NMDARs, remain poorly understood. Here, we investigate the dynamic interaction between NR2 C termini and proteins containing PSD-95/Discs-large/ZO-1 homology (PDZ) scaffold proteins at the single molecule level by using high-resolution imaging. We report that a biomimetic divalent competing ligand, mimicking the last 15 amino acids of NR2A C terminus, specifically and efficiently disrupts the interaction between 2A-NMDARs, but not 2B-NMDARs, and PDZ proteins on the time scale of minutes. Furthermore, displacing 2A-NMDARs out of synapses lead to a compensatory increase in synaptic NR2B-NMDARs, providing functional evidence that the anchoring mechanism of 2A- or 2B-NMDARs is different. These data reveal an unexpected role of the NR2 subunit divalent arrangement in providing specific anchoring within synapses, highlighting the need to study such dynamic interactions in native conditions.