Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins
Proceedings of the National Academy of Sciences. 2010-10-25; 107(45): 19561-19566
DOI: 10.1073/pnas.1002690107
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1. Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19561-6. doi:
10.1073/pnas.1002690107. Epub 2010 Oct 25.
Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ
proteins.
Bard L(1), Sainlos M, Bouchet D, Cousins S, Mikasova L, Breillat C, Stephenson
FA, Imperiali B, Choquet D, Groc L.
Author information:
(1)Laboratory for Cellular Physiology of the Synapse, Centre National de la
Recherche Scientifique, Unité Mixte de Recherche 5091, 33077 Bordeaux, France.
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.
DOI: 10.1073/pnas.1002690107
PMCID: PMC2984211
PMID: 20974938 [Indexed for MEDLINE]