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Elife. 2017 Jun 9;6. pii: e25492. doi: 10.7554/eLife.25492.

Co-agonists differentially tune GluN2B-NMDA receptor trafficking at hippocampal synapses.

Author information

1
Interdisciplinary Institute for NeuroSciences, CNRS UMR 5297, Bordeaux, France.
2
Université de Bordeaux, Bordeaux, France.
3
NSERM U862, Neurocentre Magendie, Bordeaux, France.
4
Institut de Biologie de l'ENS (IBENS), CNRS UMR 8197, INSERM U1024, Paris, France.
5
Université Aix-Marseille, CNRS CRN2M UMR 7286, Marseille, France.
6
Dipartimento di Biotecnologie e Scienze della Vita, Università degli Studi dell'Insubria, Varese, Italy.
7
The Protein Factory, Centro Interuniversitario di Biotecnologie Proteiche, Politecnico di Milano, Università degli Studi dell'Insubria, Varese, Italy.

Abstract

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.

KEYWORDS:

NMDA; neuroscience; none; subunit trafficking; synapse

PMID:
28598327
PMCID:
PMC5466419
DOI:
10.7554/eLife.25492
[Indexed for MEDLINE]
Free PMC Article

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