Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Methods Mol Biol
2017 Jan 01;1677:145-162. doi: 10.1007/978-1-4939-7321-7_7.
Show Gene links
Show Anatomy links
Selective Cell-Surface Expression of Triheteromeric NMDA Receptors.
Yi F
,
Traynelis SF
,
Hansen KB
.
???displayArticle.abstract???
The NMDA-type ionotropic glutamate receptors play pivotal roles in many brain functions, but are also involved in numerous brain disorders. Seven NMDA receptor subunits exist (GluN1, GluN2A-D, and GluN3A-B) that assemble into a diverse array of tetrameric receptor subtypes with distinct functional properties and physiological roles. Most NMDA receptors are composed of two GluN1 and two GluN2 subunits, which can assemble into four diheteromeric receptor subtypes composed of GluN1 and one type of GluN2 subunit (e.g., GluN1/2A), and presumably also six triheteromeric receptor subtypes composed of GluN1 and two different GluN2 subunits (e.g., GluN1/2A/2B). Despite accumulating evidence that a large proportion of native NMDA receptors are triheteromers, little is known about their function and pharmacology due to the lack of methods to faithfully express triheteromeric NMDA receptors in heterologous expression systems. The problem is that co-expression of GluN1 with two different GluN2 subunits generates two distinct diheteromeric receptor subtypes as well as one triheteromeric receptor subtype, thereby confounding studies on a homogenous population of triheteromeric NMDA receptors. Here, we will describe a method to selectively express recombinant triheteromeric GluN1/2A/2B receptors without interfering co-expression of diheteromeric GluN1/2A and GluN1/2B receptors. This method enables quantitative evaluation of functional and pharmacological properties of triheteromeric GluN1/2A/2B receptors, which are presumably the most abundant NMDA receptors in the adult cortex and hippocampus.
Al-Hallaq,
NMDA di-heteromeric receptor populations and associated proteins in rat hippocampus.
2007, Pubmed
Al-Hallaq,
NMDA di-heteromeric receptor populations and associated proteins in rat hippocampus.
2007,
Pubmed
Arai,
Conformations of variably linked chimeric proteins evaluated by synchrotron X-ray small-angle scattering.
2004,
Pubmed
Benveniste,
Kinetic analysis of antagonist action at N-methyl-D-aspartic acid receptors. Two binding sites each for glutamate and glycine.
1991,
Pubmed
Bettler,
Molecular structure and physiological functions of GABA(B) receptors.
2004,
Pubmed
Bossi,
Exogenous protein expression in Xenopus oocytes: basic procedures.
2007,
Pubmed
,
Xenbase
Brickley,
NR2B and NR2D subunits coassemble in cerebellar Golgi cells to form a distinct NMDA receptor subtype restricted to extrasynaptic sites.
2003,
Pubmed
Brock,
Assembly-dependent surface targeting of the heterodimeric GABAB Receptor is controlled by COPI but not 14-3-3.
2005,
Pubmed
Burmakina,
Heterodimeric coiled-coil interactions of human GABAB receptor.
2014,
Pubmed
Cathala,
Developmental profile of the changing properties of NMDA receptors at cerebellar mossy fiber-granule cell synapses.
2000,
Pubmed
Chazot,
Molecular characterization of N-methyl-D-aspartate receptors expressed in mammalian cells yields evidence for the coexistence of three subunit types within a discrete receptor molecule.
1994,
Pubmed
Cheriyan,
Pharmacology of triheteromeric N-Methyl-D-Aspartate Receptors.
2016,
Pubmed
Clements,
Activation kinetics reveal the number of glutamate and glycine binding sites on the N-methyl-D-aspartate receptor.
1991,
Pubmed
Goldin,
Maintenance of Xenopus laevis and oocyte injection.
1992,
Pubmed
,
Xenbase
Goldin,
Preparation of RNA for injection into Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Hackos,
Positive Allosteric Modulators of GluN2A-Containing NMDARs with Distinct Modes of Action and Impacts on Circuit Function.
2016,
Pubmed
Hansen,
Distinct functional and pharmacological properties of Triheteromeric GluN1/GluN2A/GluN2B NMDA receptors.
2014,
Pubmed
,
Xenbase
Hatton,
Modulation of triheteromeric NMDA receptors by N-terminal domain ligands.
2005,
Pubmed
,
Xenbase
Jespersen,
Dual-function vector for protein expression in both mammalian cells and Xenopus laevis oocytes.
2002,
Pubmed
,
Xenbase
Jones,
Functional NR2B- and NR2D-containing NMDA receptor channels in rat substantia nigra dopaminergic neurones.
2005,
Pubmed
Kammerer,
Heterodimerization of a functional GABAB receptor is mediated by parallel coiled-coil alpha-helices.
1999,
Pubmed
Karakas,
Crystal structure of a heterotetrameric NMDA receptor ion channel.
2014,
Pubmed
Khatri,
Structural determinants and mechanism of action of a GluN2C-selective NMDA receptor positive allosteric modulator.
2014,
Pubmed
,
Xenbase
Kniazeff,
Closed state of both binding domains of homodimeric mGlu receptors is required for full activity.
2004,
Pubmed
Lee,
NMDA receptor structures reveal subunit arrangement and pore architecture.
2014,
Pubmed
,
Xenbase
Leonard,
Apparent desensitization of NMDA responses in Xenopus oocytes involves calcium-dependent chloride current.
1990,
Pubmed
,
Xenbase
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Logan,
Protein kinase C modulation of recombinant NMDA receptor currents: roles for the C-terminal C1 exon and calcium ions.
1999,
Pubmed
,
Xenbase
Luo,
The majority of N-methyl-D-aspartate receptor complexes in adult rat cerebral cortex contain at least three different subunits (NR1/NR2A/NR2B).
1997,
Pubmed
Maki,
C-terminal domains of N-methyl-D-aspartic acid receptor modulate unitary channel conductance and gating.
2012,
Pubmed
Margeta-Mitrovic,
A trafficking checkpoint controls GABA(B) receptor heterodimerization.
2000,
Pubmed
,
Xenbase
Matten,
Microinjection into Xenopus oocytes.
1995,
Pubmed
,
Xenbase
Moriyoshi,
Molecular cloning and characterization of the rat NMDA receptor.
1991,
Pubmed
,
Xenbase
Piña-Crespo,
Subtypes of NMDA receptors in new-born rat hippocampal granule cells.
2002,
Pubmed
Punnakkal,
Influence of the intracellular GluN2 C-terminal domain on NMDA receptor function.
2012,
Pubmed
Pérez-Otaño,
Emerging roles of GluN3-containing NMDA receptors in the CNS.
2016,
Pubmed
Rauner,
Triheteromeric NR1/NR2A/NR2B receptors constitute the major N-methyl-D-aspartate receptor population in adult hippocampal synapses.
2011,
Pubmed
Schmidt,
Xenopus laevis oocytes endogenously express all subunits of the ionotropic glutamate receptor family.
2009,
Pubmed
,
Xenbase
Schmidt,
Molecular and functional characterization of Xenopus laevis N-methyl-d-aspartate receptors.
2009,
Pubmed
,
Xenbase
Serraz,
Altered zinc sensitivity of NMDA receptors harboring clinically-relevant mutations.
2016,
Pubmed
,
Xenbase
Sheng,
Changing subunit composition of heteromeric NMDA receptors during development of rat cortex.
1994,
Pubmed
Stroebel,
Controlling NMDA receptor subunit composition using ectopic retention signals.
2014,
Pubmed
,
Xenbase
Stühmer,
Electrophysiologic recordings from Xenopus oocytes.
1998,
Pubmed
,
Xenbase
Swanger,
NMDA Receptors Containing the GluN2D Subunit Control Neuronal Function in the Subthalamic Nucleus.
2015,
Pubmed
Terhag,
Cave Canalem: how endogenous ion channels may interfere with heterologous expression in Xenopus oocytes.
2010,
Pubmed
,
Xenbase
Tovar,
Triheteromeric NMDA receptors at hippocampal synapses.
2013,
Pubmed
Traynelis,
Glutamate receptor ion channels: structure, regulation, and function.
2010,
Pubmed
Ulbrich,
Subunit counting in membrane-bound proteins.
2007,
Pubmed
,
Xenbase
Vicini,
Functional and pharmacological differences between recombinant N-methyl-D-aspartate receptors.
1998,
Pubmed
Williams,
Ifenprodil discriminates subtypes of the N-methyl-D-aspartate receptor: selectivity and mechanisms at recombinant heteromeric receptors.
1993,
Pubmed
,
Xenbase
Yi,
Structural Basis for Negative Allosteric Modulation of GluN2A-Containing NMDA Receptors.
2016,
Pubmed
,
Xenbase
Yuan,
Functional analysis of a de novo GRIN2A missense mutation associated with early-onset epileptic encephalopathy.
2014,
Pubmed
Zerangue,
Analysis of endoplasmic reticulum trafficking signals by combinatorial screening in mammalian cells.
2001,
Pubmed
Zheng,
Ca2+ influx amplifies protein kinase C potentiation of recombinant NMDA receptors.
1997,
Pubmed
,
Xenbase
