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

Abstract 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...

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Autores principales:	Kristyna Skrenkova, Katarina Hemelikova, Marharyta Kolcheva, Stepan Kortus, Martina Kaniakova, Barbora Krausova, Martin Horak
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f472834e09084930aa0fbf6223cd8223
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spelling	oai:doaj.org-article:f472834e09084930aa0fbf6223cd82232021-12-02T15:08:31ZStructural features in the glycine-binding sites of the GluN1 and GluN3A subunits regulate the surface delivery of NMDA receptors10.1038/s41598-019-48845-32045-2322https://doaj.org/article/f472834e09084930aa0fbf6223cd82232019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48845-3https://doaj.org/toc/2045-2322Abstract 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.Kristyna SkrenkovaKatarina HemelikovaMarharyta KolchevaStepan KortusMartina KaniakovaBarbora KrausovaMartin HorakNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-16 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kristyna Skrenkova Katarina Hemelikova Marharyta Kolcheva Stepan Kortus Martina Kaniakova Barbora Krausova Martin Horak Structural features in the glycine-binding sites of the GluN1 and GluN3A subunits regulate the surface delivery of NMDA receptors
description	Abstract 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.
format	article
author	Kristyna Skrenkova Katarina Hemelikova Marharyta Kolcheva Stepan Kortus Martina Kaniakova Barbora Krausova Martin Horak
author_facet	Kristyna Skrenkova Katarina Hemelikova Marharyta Kolcheva Stepan Kortus Martina Kaniakova Barbora Krausova Martin Horak
author_sort	Kristyna Skrenkova
title	Structural features in the glycine-binding sites of the GluN1 and GluN3A subunits regulate the surface delivery of NMDA receptors
title_short	Structural features in the glycine-binding sites of the GluN1 and GluN3A subunits regulate the surface delivery of NMDA receptors
title_full	Structural features in the glycine-binding sites of the GluN1 and GluN3A subunits regulate the surface delivery of NMDA receptors
title_fullStr	Structural features in the glycine-binding sites of the GluN1 and GluN3A subunits regulate the surface delivery of NMDA receptors
title_full_unstemmed	Structural features in the glycine-binding sites of the GluN1 and GluN3A subunits regulate the surface delivery of NMDA receptors
title_sort	structural features in the glycine-binding sites of the glun1 and glun3a subunits regulate the surface delivery of nmda receptors
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/f472834e09084930aa0fbf6223cd8223
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Structural features in the glycine-binding sites of the GluN1 and GluN3A subunits regulate the surface delivery of NMDA receptors

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