Structure, function, and allosteric modulation of NMDA receptors

Kasper B. Hansen; Feng Yi; Riley E. Perszyk; Hiro Furukawa; Lonnie P. Wollmuth; Alasdair J. Gibb; Stephen F. Traynelis

doi:10.1085/jgp.201812032

Structure, function, and allosteric modulation of NMDA receptors

Kasper B. Hansen
, Feng Yi
, Riley E. Perszyk
, Hiro Furukawa
, Lonnie P. Wollmuth
, Alasdair J. Gibb
, Stephen F. Traynelis

Research output: Contribution to journal › Review article › peer-review

465 Scopus citations

Abstract

NMDA-type glutamate receptors are ligand-gated ion channels that mediate a Ca²⁺-permeable component of excitatory neurotransmission in the central nervous system (CNS). They are expressed throughout the CNS and play key physiological roles in synaptic function, such as synaptic plasticity, learning, and memory. NMDA receptors are also implicated in the pathophysiology of several CNS disorders and more recently have been identified as a locus for disease-associated genomic variation. NMDA receptors exist as a diverse array of subtypes formed by variation in assembly of seven subunits (GluN1, GluN2A-D, and GluN3A-B) into tetrameric receptor complexes. These NMDA receptor subtypes show unique structural features that account for their distinct functional and pharmacological properties allowing precise tuning of their physiological roles. Here, we review the relationship between NMDA receptor structure and function with an emphasis on emerging atomic resolution structures, which begin to explain unique features of this receptor.

Original language	English
Pages (from-to)	1081-1105
Number of pages	25
Journal	Journal of General Physiology
Volume	150
Issue number	8
DOIs	https://doi.org/10.1085/jgp.201812032
State	Published - Aug 1 2018

Funding

This work was supported by grants from National Institutes of Health to S.F. Traynelis (NS036654 and NS065371), K.B. Hansen (GM103546 and NS097536), and L.P. Wollmuth (NS088479). S.F. Traynelis is a consultant for Janssen Pharmaceuticals, Inc., the principal investigator on a research grant awarded to Emory University from Janssen Pharmaceuticals, a member of the Scientific Advisory Board for Sage Therapeutics, and co-founder of NeurOp, Inc. K.B. Hansen is the principal investigator on a research grant awarded to University of Montana from Janssen Pharmaceuticals. The other authors declare no competing financial interests. Author contributions: All authors wrote the manuscript. Lesley C. Anson served as editor.

Funder number
NS036654, NS065371
R01MH085926

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10.1085/jgp.201812032

Cite this

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title = "Structure, function, and allosteric modulation of NMDA receptors",

abstract = "NMDA-type glutamate receptors are ligand-gated ion channels that mediate a Ca2+-permeable component of excitatory neurotransmission in the central nervous system (CNS). They are expressed throughout the CNS and play key physiological roles in synaptic function, such as synaptic plasticity, learning, and memory. NMDA receptors are also implicated in the pathophysiology of several CNS disorders and more recently have been identified as a locus for disease-associated genomic variation. NMDA receptors exist as a diverse array of subtypes formed by variation in assembly of seven subunits (GluN1, GluN2A-D, and GluN3A-B) into tetrameric receptor complexes. These NMDA receptor subtypes show unique structural features that account for their distinct functional and pharmacological properties allowing precise tuning of their physiological roles. Here, we review the relationship between NMDA receptor structure and function with an emphasis on emerging atomic resolution structures, which begin to explain unique features of this receptor.",

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AU - Hansen, Kasper B.

AU - Yi, Feng

AU - Perszyk, Riley E.

AU - Furukawa, Hiro

AU - Wollmuth, Lonnie P.

AU - Gibb, Alasdair J.

AU - Traynelis, Stephen F.

PY - 2018/8/1

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N2 - NMDA-type glutamate receptors are ligand-gated ion channels that mediate a Ca2+-permeable component of excitatory neurotransmission in the central nervous system (CNS). They are expressed throughout the CNS and play key physiological roles in synaptic function, such as synaptic plasticity, learning, and memory. NMDA receptors are also implicated in the pathophysiology of several CNS disorders and more recently have been identified as a locus for disease-associated genomic variation. NMDA receptors exist as a diverse array of subtypes formed by variation in assembly of seven subunits (GluN1, GluN2A-D, and GluN3A-B) into tetrameric receptor complexes. These NMDA receptor subtypes show unique structural features that account for their distinct functional and pharmacological properties allowing precise tuning of their physiological roles. Here, we review the relationship between NMDA receptor structure and function with an emphasis on emerging atomic resolution structures, which begin to explain unique features of this receptor.

AB - NMDA-type glutamate receptors are ligand-gated ion channels that mediate a Ca2+-permeable component of excitatory neurotransmission in the central nervous system (CNS). They are expressed throughout the CNS and play key physiological roles in synaptic function, such as synaptic plasticity, learning, and memory. NMDA receptors are also implicated in the pathophysiology of several CNS disorders and more recently have been identified as a locus for disease-associated genomic variation. NMDA receptors exist as a diverse array of subtypes formed by variation in assembly of seven subunits (GluN1, GluN2A-D, and GluN3A-B) into tetrameric receptor complexes. These NMDA receptor subtypes show unique structural features that account for their distinct functional and pharmacological properties allowing precise tuning of their physiological roles. Here, we review the relationship between NMDA receptor structure and function with an emphasis on emerging atomic resolution structures, which begin to explain unique features of this receptor.

UR - https://www.scopus.com/pages/publications/85053843399

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SN - 0022-1295

VL - 150

SP - 1081

EP - 1105

JO - Journal of General Physiology

JF - Journal of General Physiology

IS - 8

ER -

Structure, function, and allosteric modulation of NMDA receptors

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