Structural features in the glycine-binding sites of the GluN1 and GluN3A subunits regulate the surface delivery of NMDA receptors

0508277 - ÚEM 2020 RIV GB eng J - Journal Article
Skřenková, Kristýna - Hemelíková, Katarína - Kolcheva, Marharyta - Kortus, Štěpán - Kaniaková, Martina - Hrčka Krausová, Barbora - Horák, Martin
Structural features in the glycine-binding sites of the GluN1 and GluN3A subunits regulate the surface delivery of NMDA receptors.
Scientific Reports. Roč. 9, aug. (2019), č. článku 12303. ISSN 2045-2322. E-ISSN 2045-2322
R&D Projects: GA MŠMT(CZ) LM2015062
Institutional support: RVO:68378041
Keywords : methyl-d-aspartate * endoplasmic-reticulum * molecular determinants * synaptic plasticity
OECD category: Neurosciences (including psychophysiology
Impact factor: 3.998, year: 2019
Method of publishing: Open access
https://www.nature.com/articles/s41598-019-48845-3

N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors that play an essential role in mediating excitatory neurotransmission in the mammalian central nervous system (CNS). Functional NMDARs are tetramers composed of GluN1, GluN2A-D, and/ or GluN3A-B subunits, giving rise to a wide variety of NMDAR subtypes with unique functional properties. Here, we examined the surface delivery and functional properties of NMDARs containing mutations in the glycine-binding sites in GluN1 and GluN3A subunits expressed in mammalian cell lines and primary rat hippocampal neurons. We found that the structural features of the glycine-binding sites in both GluN1 and GluN3A subunits are correlated with receptor forward trafficking to the cell surface. In addition, we found that a potentially clinically relevant mutation in the glycine-binding site of the human GluN3A subunit significantly reduces surface delivery of NMDARs. Taken together, these findings provide novel insight into how NMDARs are regulated by their glycine-binding sites and may provide important information regarding the role of NMDARs in both physiological and pathophysiological processes in the mammalian CNS.
Permanent Link: http://hdl.handle.net/11104/0299233