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

Bard, L., Sainlos, M., Bouchet, D., Cousins, S.L., Mikasova, L., Breillat, C., Stephenson, F.A., Imperiali, B., Choquet, D. and Groc, L. (2010) Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins. Proceedings of the National Academy of Sciences, 107 (45). pp. 19561-19566. 10.1073/pnas.1002690107.

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DOI: 10.1073/pnas.1002690107

Abstract

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.

Item Type:Article
Uncontrolled Keywords:lateral diffusion glutamate receptor trafficking biomimetic multivalent ligand development
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:2487
Journal or Publication Title:Proceedings of the National Academy of Sciences
Deposited By:Library Staff
Deposited On:24 Nov 2011 09:29
Last Modified:10 May 2012 17:07

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