Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins
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 interactio...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2014
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| Online Access: | http://hdl.handle.net/1721.1/84594 https://orcid.org/0000-0002-5749-7869 |
| _version_ | 1826216217255346176 |
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| author | Bard, Lucie Sainlos, Matthieu Bouchet, Delphine Cousins, Sarah Mikasova, Lenka Breillat, Christelle Stephenson, F. Anne Imperiali, Barbara Choquet, Daniel Groc, Laurent |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Bard, Lucie Sainlos, Matthieu Bouchet, Delphine Cousins, Sarah Mikasova, Lenka Breillat, Christelle Stephenson, F. Anne Imperiali, Barbara Choquet, Daniel Groc, Laurent |
| author_sort | Bard, Lucie |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T16:43:50Z |
| format | Article |
| id | mit-1721.1/84594 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:43:50Z |
| publishDate | 2014 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/845942022-09-29T21:04:51Z Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins Bard, Lucie Sainlos, Matthieu Bouchet, Delphine Cousins, Sarah Mikasova, Lenka Breillat, Christelle Stephenson, F. Anne Imperiali, Barbara Choquet, Daniel Groc, Laurent Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemistry Sainlos, Matthieu Imperiali, Barbara 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. 2014-01-27T18:56:07Z 2014-01-27T18:56:07Z 2010-10 2010-03 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/84594 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. https://orcid.org/0000-0002-5749-7869 en_US http://dx.doi.org/10.1073/pnas.1002690107 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Bard, Lucie Sainlos, Matthieu Bouchet, Delphine Cousins, Sarah Mikasova, Lenka Breillat, Christelle Stephenson, F. Anne Imperiali, Barbara Choquet, Daniel Groc, Laurent Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins |
| title | Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins |
| title_full | Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins |
| title_fullStr | Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins |
| title_full_unstemmed | Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins |
| title_short | Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins |
| title_sort | dynamic and specific interaction between synaptic nr2 nmda receptor and pdz proteins |
| url | http://hdl.handle.net/1721.1/84594 https://orcid.org/0000-0002-5749-7869 |
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