Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins
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Author(s)
Bard, Lucie
Sainlos, Matthieu
Bouchet, Delphine
Cousins, Sarah
Mikasova, Lenka
Breillat, Christelle
Stephenson, F. Anne
Imperiali, Barbara
Choquet, Daniel
Groc, Laurent
Date Issued
October 2010
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Bard, L., M. Sainlos, D. Bouchet, S. Cousins, L. Mikasova, C. Breillat, F. A. Stephenson, B. Imperiali, D. Choquet, and L. Groc. “Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins.” Proceedings of the National Academy of Sciences 107, no. 45 (November 9, 2010): 19561-19566.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1073/pnas.1002690107
