PMID- 28598327 OWN - NLM STAT- MEDLINE DCOM- 20180219 LR - 20181113 IS - 2050-084X (Electronic) IS - 2050-084X (Linking) VI - 6 DP - 2017 Jun 9 TI - Co-agonists differentially tune GluN2B-NMDA receptor trafficking at hippocampal synapses. LID - e25492 [pii] LID - 10.7554/eLife.25492 [doi] AB - The subunit composition of synaptic NMDA receptors (NMDAR), such as the relative content of GluN2A- and GluN2B-containing receptors, greatly influences the glutamate synaptic transmission. Receptor co-agonists, glycine and D-serine, have intriguingly emerged as potential regulators of the receptor trafficking in addition to their requirement for its activation. Using a combination of single-molecule imaging, biochemistry and electrophysiology, we show that glycine and D-serine relative availability at rat hippocampal glutamatergic synapses regulate the trafficking and synaptic content of NMDAR subtypes. Acute manipulations of co-agonist levels, both ex vivo and in vitro, unveil that D-serine alter the membrane dynamics and content of GluN2B-NMDAR, but not GluN2A-NMDAR, at synapses through a process requiring PDZ binding scaffold partners. In addition, using FRET-based FLIM approach, we demonstrate that D-serine rapidly induces a conformational change of the GluN1 subunit intracellular C-terminus domain. Together our data fuels the view that the extracellular microenvironment regulates synaptic NMDAR signaling. FAU - Ferreira, Joana S AU - Ferreira JS AUID- ORCID: 0000-0002-1049-8063 AD - Interdisciplinary Institute for NeuroSciences, CNRS UMR 5297, Bordeaux, France. AD - Universite de Bordeaux, Bordeaux, France. FAU - Papouin, Thomas AU - Papouin T AD - Universite de Bordeaux, Bordeaux, France. AD - NSERM U862, Neurocentre Magendie, Bordeaux, France. FAU - Ladepeche, Laurent AU - Ladepeche L AD - Interdisciplinary Institute for NeuroSciences, CNRS UMR 5297, Bordeaux, France. AD - Universite de Bordeaux, Bordeaux, France. FAU - Yao, Andrea AU - Yao A AD - Institut de Biologie de l'ENS (IBENS), CNRS UMR 8197, INSERM U1024, Paris, France. FAU - Langlais, Valentin C AU - Langlais VC AD - Universite de Bordeaux, Bordeaux, France. AD - NSERM U862, Neurocentre Magendie, Bordeaux, France. FAU - Bouchet, Delphine AU - Bouchet D AD - Interdisciplinary Institute for NeuroSciences, CNRS UMR 5297, Bordeaux, France. AD - Universite de Bordeaux, Bordeaux, France. FAU - Dulong, Jerome AU - Dulong J AD - Universite de Bordeaux, Bordeaux, France. AD - NSERM U862, Neurocentre Magendie, Bordeaux, France. FAU - Mothet, Jean-Pierre AU - Mothet JP AD - Universite Aix-Marseille, CNRS CRN2M UMR 7286, Marseille, France. FAU - Sacchi, Silvia AU - Sacchi S AD - Dipartimento di Biotecnologie e Scienze della Vita, Universita degli Studi dell'Insubria, Varese, Italy. AD - The Protein Factory, Centro Interuniversitario di Biotecnologie Proteiche, Politecnico di Milano, Universita degli Studi dell'Insubria, Varese, Italy. FAU - Pollegioni, Loredano AU - Pollegioni L AD - Dipartimento di Biotecnologie e Scienze della Vita, Universita degli Studi dell'Insubria, Varese, Italy. AD - The Protein Factory, Centro Interuniversitario di Biotecnologie Proteiche, Politecnico di Milano, Universita degli Studi dell'Insubria, Varese, Italy. FAU - Paoletti, Pierre AU - Paoletti P AUID- ORCID: 0000-0002-3681-4845 AD - Institut de Biologie de l'ENS (IBENS), CNRS UMR 8197, INSERM U1024, Paris, France. FAU - Oliet, Stephane Henri Richard AU - Oliet SHR AUID- ORCID: 0000-0003-0595-9029 AD - Universite de Bordeaux, Bordeaux, France. AD - NSERM U862, Neurocentre Magendie, Bordeaux, France. FAU - Groc, Laurent AU - Groc L AUID- ORCID: 0000-0003-1814-8145 AD - Interdisciplinary Institute for NeuroSciences, CNRS UMR 5297, Bordeaux, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170609 PL - England TA - Elife JT - eLife JID - 101579614 RN - 0 (NR2B NMDA receptor) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 452VLY9402 (Serine) RN - TE7660XO1C (Glycine) SB - IM MH - Animals MH - Glycine/*metabolism MH - Hippocampus/*physiology MH - Rats MH - Receptors, N-Methyl-D-Aspartate/*agonists MH - Serine/*metabolism MH - Synapses/*physiology PMC - PMC5466419 OTO - NOTNLM OT - NMDA OT - neuroscience OT - none OT - subunit trafficking OT - synapse COIS- The authors declare that no competing interests exist. EDAT- 2017/06/10 06:00 MHDA- 2018/02/20 06:00 PMCR- 2017/06/10 CRDT- 2017/06/10 06:00 PHST- 2017/01/26 00:00 [received] PHST- 2017/05/29 00:00 [accepted] PHST- 2017/06/10 06:00 [entrez] PHST- 2017/06/10 06:00 [pubmed] PHST- 2018/02/20 06:00 [medline] PHST- 2017/06/10 00:00 [pmc-release] AID - e25492 [pii] AID - 25492 [pii] AID - 10.7554/eLife.25492 [doi] PST - epublish SO - Elife. 2017 Jun 9;6:e25492. doi: 10.7554/eLife.25492.