Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins

被引：81

作者：

Bard, Lucie ^{[1
,2
]}

Sainlos, Matthieu ^{[1
,3
,4
]}

Bouchet, Delphine ^{[1
,2
]}

Cousins, Sarah ^{[5
]}

Mikasova, Lenka ^{[1
,2
]}

Breillat, Christelle ^{[1
,2
]}

Stephenson, F. Anne ^{[5
]}

Imperiali, Barbara ^{[3
,4
]}

Choquet, Daniel ^{[1
,2
]}

Groc, Laurent ^{[1
,2
]}

机构：

[1] CNRS, Lab Cellular Physiol Synapse, Unite Mixte Rech 5091, F-33077 Bordeaux, France

[2] Univ Bordeaux, F-33077 Bordeaux, France

[3] MIT, Dept Chem, Cambridge, MA 02139 USA

[4] MIT, Dept Biol, Cambridge, MA 02139 USA

[5] Univ London, Sch Pharm, London WC1N 1AX, England

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 45期

基金：

英国生物技术与生命科学研究理事会; 欧洲研究理事会;

关键词：

lateral diffusion; glutamate receptor; trafficking; biomimetic multivalent ligand; development; NMDA-RECEPTORS; NR2; SUBUNITS; TRAFFICKING; DOMAINS; LOCALIZATION; PSD-95; EXPRESSION; PLASTICITY; SUBTYPES; CHANNEL;

D O I：

10.1073/pnas.1002690107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：19561 / 19566

页数：6

共 36 条

[1]

Treatment of ischemic brain damage by perturbing NMDA receptor-PSD-95 protein interactions [J].