TY - JOUR
T1 - Co-agonists differentially tune GluN2B-NMDA receptor trafficking at hippocampal synapses
AU - Ferreira, Joana S.
AU - Papouin, Thomas
AU - Ladépêche, Laurent
AU - Yao, Andrea
AU - Langlais, Valentin C.
AU - Bouchet, Delphine
AU - Dulong, Jérôme
AU - Mothet, Jean Pierre
AU - Sacchi, Silvia
AU - Pollegioni, Loredano
AU - Paoletti, Pierre
AU - Richard Oliet, Stéphane Henri
AU - Groc, Laurent
N1 - Funding Information:
Agence Nationale de la Recherche Neuroscience Program Laurent Groc The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Publisher Copyright:
© Ferreira et al.
PY - 2017/6/9
Y1 - 2017/6/9
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85021170367&partnerID=8YFLogxK
U2 - 10.7554/eLife.25492
DO - 10.7554/eLife.25492
M3 - Article
C2 - 28598327
AN - SCOPUS:85021170367
SN - 2050-084X
VL - 6
JO - eLife
JF - eLife
M1 - e25492
ER -