 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, April 15, 1998, 18(8):2954-2961
Evidence for a Tetrameric Structure of Recombinant NMDA Receptors
Bodo Laube, Jochen Kuhse, and Heinrich Betz Department of Neurochemistry, Max-Planck-Institute for Brain Research, 60528 Frankfurt/Main, Germany
The amino acids L-glutamate and glycine are essential agonists of the excitatory NMDA receptor, a subtype of the ionotropic glutamate receptor family. The native NMDA receptor is composed of two types of homologous membrane-spanning subunits, NR1 and NR2. Here, the numbers of glycine-binding NR1 and glutamate-binding NR2 subunits in the NMDA receptor hetero-oligomer were determined by coexpressing the wild-type (wt) NR1 with the low-affinity mutant NR1Q387K, and the wt NR2B with the low-affinity mutant NR2BE387A, subunits in Xenopus oocytes. In both cases, analysis of the resulting dose-response curves revealed three independent components of glycine and glutamate sensitivity. These correspond to the respective wild-type and mutant affinities and an additional intermediate hybrid affinity, indicating the existence of three discrete receptor populations. Binomial analysis of these data indicates the presence of two glycine and two glutamate binding subunits in the functional receptor. In addition, we analyzed the inhibitory effects of the negative dominant NR1R505K and NR2BR493K mutants on maximal inducible whole-cell currents of wt NR1/NR2B receptors. The inhibition profiles obtained on expression of increasing amounts of these mutant proteins again were fitted best by assuming an incorporation of two NR1 and two NR2 subunits into the receptor hetero-oligomer. Our data are consistent with NMDA receptors being tetrameric proteins that are composed of four homologous subunits.
Key words: mutagenesis; subunit stoichiometry; NMDA receptor; glutamate; channel assembly; electrophysiology; agonist affinity; Xenopus oocyte
Copyright © 1998 Society for Neuroscience 0270-6474/98/1882954-08$05.00/0
This article has been cited by other articles:
J. P. Ridge, A. M.-C. Ho, and P. R. Dodd
Sex Differences in NMDA Receptor Expression in Human Alcoholics
Alcohol Alcohol., November 1, 2009; 44(6): 594 - 601.
[Abstract] [Full Text] [PDF]
L. Wise-Faberowski, P. N. Robinson, S. Rich, and D. S. Warner
Oxygen and Glucose Deprivation in an Organotypic Hippocampal Slice Model of the Developing Rat Brain: The Effects on N-Methyl-d-Aspartate Subunit Composition
Anesth. Analg., July 1, 2009; 109(1): 205 - 210.
[Abstract] [Full Text] [PDF]
S.-H. Yeh, J.-J. Hung, P.-W. Gean, and W.-C. Chang
Hypoxia-Inducible Factor-1{alpha} Protects Cultured Cortical Neurons from Lipopolysaccharide-Induced Cell Death via Regulation of NR1 Expression
J. Neurosci., December 24, 2008; 28(52): 14259 - 14270.
[Abstract] [Full Text] [PDF]
J. Xu, Y. Liu, and G.-Y. Zhang
Neuroprotection of GluR5-containing Kainate Receptor Activation against Ischemic Brain Injury through Decreasing Tyrosine Phosphorylation of N-Methyl-D-aspartate Receptors Mediated by Src Kinase
J. Biol. Chem., October 24, 2008; 283(43): 29355 - 29366.
[Abstract] [Full Text] [PDF]
J. de Marchena, A. C. Roberts, P. G. Middlebrooks, V. Valakh, K. Yashiro, L. R. Wilfley, and B. D. Philpot
NMDA Receptor Antagonists Reveal Age-Dependent Differences in the Properties of Visual Cortical Plasticity
J Neurophysiol, October 1, 2008; 100(4): 1936 - 1948.
[Abstract] [Full Text] [PDF]
M. H. Ulbrich and E. Y. Isacoff
Rules of engagement for NMDA receptor subunits
PNAS, September 16, 2008; 105(37): 14163 - 14168.
[Abstract] [Full Text] [PDF]
C. Madry, H. Betz, J. R. P. Geiger, and B. Laube
Supralinear potentiation of NR1/NR3A excitatory glycine receptors by Zn2+ and NR1 antagonist
PNAS, August 26, 2008; 105(34): 12563 - 12568.
[Abstract] [Full Text] [PDF]
J. L. Brigman, M. Feyder, L. M. Saksida, T. J. Bussey, M. Mishina, and A. Holmes
Impaired discrimination learning in mice lacking the NMDA receptor NR2A subunit
Learn. Mem., January 28, 2008; 15(2): 50 - 54.
[Abstract] [Full Text] [PDF]
T. Schuler, I. Mesic, C. Madry, I. Bartholomaus, and B. Laube
Formation of NR1/NR2 and NR1/NR3 Heterodimers Constitutes the Initial Step in N-Methyl-D-aspartate Receptor Assembly
J. Biol. Chem., January 4, 2008; 283(1): 37 - 46.
[Abstract] [Full Text] [PDF]
C. Madry, I. Mesic, H. Betz, and B. Laube
The N-Terminal Domains of both NR1 and NR2 Subunits Determine Allosteric Zn2+ Inhibition and Glycine Affinity of N-Methyl-D-aspartate Receptors
Mol. Pharmacol., December 1, 2007; 72(6): 1535 - 1544.
[Abstract] [Full Text] [PDF]
V. A. Alvarez, D. A. Ridenour, and B. L. Sabatini
Distinct Structural and Ionotropic Roles of NMDA Receptors in Controlling Spine and Synapse Stability
J. Neurosci., July 11, 2007; 27(28): 7365 - 7376.
[Abstract] [Full Text] [PDF]
W. Maier, R. Schemm, C. Grewer, and B. Laube
Disruption of Interdomain Interactions in the Glutamate Binding Pocket Affects Differentially Agonist Affinity and Efficacy of N-methyl-D-aspartate Receptor Activation
J. Biol. Chem., January 19, 2007; 282(3): 1863 - 1872.
[Abstract] [Full Text] [PDF]
J. Ogata, M. Shiraishi, T. Namba, C. T. Smothers, J. J. Woodward, and R. A. Harris
Effects of Anesthetics on Mutant N-Methyl-D-Aspartate Receptors Expressed in Xenopus Oocytes
J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 434 - 443.
[Abstract] [Full Text] [PDF]
M. W. Fleck
Glutamate Receptors and Endoplasmic Reticulum Quality Control: Looking beneath the Surface
Neuroscientist, June 1, 2006; 12(3): 232 - 244.
[Abstract] [PDF]
G. Imataka, J. Hirato, Y. Nakazato, and H. Yamanouchi
Expression of the N-Methyl-D-Aspartate Receptor Subunit R1 in the Developing Human Hippocampus
J Child Neurol, March 1, 2006; 21(3): 236 - 240.
[Abstract] [PDF]
Y. Wu, R. Kawakami, Y. Shinohara, M. Fukaya, K. Sakimura, M. Mishina, M. Watanabe, I. Ito, and R. Shigemoto
Target-Cell-Specific Left-Right Asymmetry of NMDA Receptor Content in Schaffer Collateral Synapses in {epsilon}1/NR2A Knock-Out Mice
J. Neurosci., October 5, 2005; 25(40): 9213 - 9226.
[Abstract] [Full Text] [PDF]
M. Petrovic, M. Sedlacek, M. Horak, H. Chodounska, and L. Vyklicky Jr
20-Oxo-5{beta}-Pregnan-3{alpha}-yl Sulfate Is a Use-Dependent NMDA Receptor Inhibitor
J. Neurosci., September 14, 2005; 25(37): 8439 - 8450.
[Abstract] [Full Text] [PDF]
H. Yuan, K. Erreger, S. M. Dravid, and S. F. Traynelis
Conserved Structural and Functional Control of N-Methyl-D-aspartate Receptor Gating by Transmembrane Domain M3
J. Biol. Chem., August 19, 2005; 280(33): 29708 - 29716.
[Abstract] [Full Text] [PDF]
E. A. Waxman and D. R. Lynch
N-Methyl-D-aspartate Receptor Subtype Mediated Bidirectional Control of p38 Mitogen-activated Protein Kinase
J. Biol. Chem., August 12, 2005; 280(32): 29322 - 29333.
[Abstract] [Full Text] [PDF]
S. Qiu, Y.-l. Hua, F. Yang, Y.-z. Chen, and J.-h. Luo
Subunit Assembly of N-Methyl-D-aspartate Receptors Analyzed by Fluorescence Resonance Energy Transfer
J. Biol. Chem., July 1, 2005; 280(26): 24923 - 24930.
[Abstract] [Full Text] [PDF]
B. Miao, X.-H. Yin, D.-S. Pei, Q.-G. Zhang, and G.-Y. Zhang
Neuroprotective Effects of Preconditioning Ischemia on Ischemic Brain Injury through Down-regulating Activation of JNK1/2 via N-Methyl-D-aspartate Receptor-mediated Akt1 Activation
J. Biol. Chem., June 10, 2005; 280(23): 21693 - 21699.
[Abstract] [Full Text] [PDF]
A. B. Sanchez and J. C. de la Torre
Genetic and Biochemical Evidence for an Oligomeric Structure of the Functional L Polymerase of the Prototypic Arenavirus Lymphocytic Choriomeningitis Virus
J. Virol., June 1, 2005; 79(11): 7262 - 7268.
[Abstract] [Full Text] [PDF]
L. Kinarsky, B. Feng, D. A. Skifter, R. M. Morley, S. Sherman, D. E. Jane, and D. T. Monaghan
Identification of Subunit- and Antagonist-Specific Amino Acid Residues in the N-Methyl-D-aspartate Receptor Glutamate-Binding Pocket
J. Pharmacol. Exp. Ther., June 1, 2005; 313(3): 1066 - 1074.
[Abstract] [Full Text] [PDF]
G. C. Bird, L. L. Lash, J. S. Han, X. Zou, W. D. Willis, and V. Neugebauer
Protein kinase A-dependent enhanced NMDA receptor function in pain-related synaptic plasticity in rat amygdala neurones
J. Physiol., May 1, 2005; 564(3): 907 - 921.
[Abstract] [Full Text] [PDF]
G. Qin, T. Schwarz, R. J. Kittel, A. Schmid, T. M. Rasse, D. Kappei, E. Ponimaskin, M. Heckmann, and S. J. Sigrist
Four Different Subunits Are Essential for Expressing the Synaptic Glutamate Receptor at Neuromuscular Junctions of Drosophila
J. Neurosci., March 23, 2005; 25(12): 3209 - 3218.
[Abstract] [Full Text] [PDF]
A. Frandsen, D. S. Pickering, B. Vestergaard, C. Kasper, B. B. Nielsen, J. R. Greenwood, G. Campiani, C. Fattorusso, M. Gajhede, A. Schousboe, et al.
Tyr702 Is an Important Determinant of Agonist Binding and Domain Closure of the Ligand-Binding Core of GluR2
Mol. Pharmacol., March 1, 2005; 67(3): 703 - 713.
[Abstract] [Full Text] [PDF]
S. G. Cull-Candy and D. N. Leszkiewicz
Role of Distinct NMDA Receptor Subtypes at Central Synapses
Sci. Signal., October 19, 2004; 2004(255): re16 - re16.
[Abstract] [Full Text] [PDF]
P. V. Massey, B. E. Johnson, P. R. Moult, Y. P. Auberson, M. W. Brown, E. Molnar, G. L. Collingridge, and Z. I. Bashir
Differential Roles of NR2A and NR2B-Containing NMDA Receptors in Cortical Long-Term Potentiation and Long-Term Depression
J. Neurosci., September 8, 2004; 24(36): 7821 - 7828.
[Abstract] [Full Text] [PDF]
A. Kloda, J. D. Clements, R. J. Lewis, and D. J. Adams
Adenosine Triphosphate Acts as Both a Competitive Antagonist and a Positive Allosteric Modulator at Recombinant N-Methyl-D-aspartate Receptors
Mol. Pharmacol., June 1, 2004; 65(6): 1386 - 1396.
[Abstract] [Full Text] [PDF]
R. L. McFEETERS and R. E. OSWALD
Emerging structural explanations of ionotropic glutamate receptor function
FASEB J, March 1, 2004; 18(3): 428 - 438.
[Abstract] [Full Text] [PDF]
H. CEULEMANS and M. BOLLEN
Functional Diversity of Protein Phosphatase-1, a Cellular Economizer and Reset Button
Physiol Rev, January 1, 2004; 84(1): 1 - 39.
[Abstract] [Full Text] [PDF]
N. O. Dalby and I. Mody
Activation of NMDA Receptors in Rat Dentate Gyrus Granule Cells by Spontaneous and Evoked Transmitter Release
J Neurophysiol, August 1, 2003; 90(2): 786 - 797.
[Abstract] [Full Text] [PDF]
M. Lopez de Armentia and P. Sah
Development and Subunit Composition of Synaptic NMDA Receptors in the Amygdala: NR2B Synapses in the Adult Central Amygdala
J. Neurosci., July 30, 2003; 23(17): 6876 - 6883.
[Abstract] [Full Text] [PDF]
Z. Ren, N. J. Riley, E. P. Garcia, J. M. Sanders, G. T. Swanson, and J. Marshall
Multiple Trafficking Signals Regulate Kainate Receptor KA2 Subunit Surface Expression
J. Neurosci., July 23, 2003; 23(16): 6608 - 6616.
[Abstract] [Full Text] [PDF]
B. Foucaud, B. Laube, R. Schemm, A. Kreimeyer, M. Goeldner, and H. Betz
Structural Model of the N-Methyl-D-aspartate Receptor Glycine Site Probed by Site-directed Chemical Coupling
J. Biol. Chem., June 20, 2003; 278(26): 24011 - 24017.
[Abstract] [Full Text] [PDF]
S. G. Brickley, C. Misra, M. H. S. Mok, M. Mishina, and S. G. Cull-Candy
NR2B and NR2D Subunits Coassemble in Cerebellar Golgi Cells to Form a Distinct NMDA Receptor Subtype Restricted to Extrasynaptic Sites
J. Neurosci., June 15, 2003; 23(12): 4958 - 4966.
[Abstract] [Full Text] [PDF]
S. Schorge and D. Colquhoun
Studies of NMDA Receptor Function and Stoichiometry with Truncated and Tandem Subunits
J. Neurosci., February 15, 2003; 23(4): 1151 - 1158.
[Abstract] [Full Text] [PDF]
M. W. Fleck, E. Cornell, and S. J. Mah
Amino-Acid Residues Involved in Glutamate Receptor 6 Kainate Receptor Gating and Desensitization
J. Neurosci., February 15, 2003; 23(4): 1219 - 1227.
[Abstract] [Full Text] [PDF]
E. Harvey-Girard and R. J. Dunn
Excitatory Amino Acid Receptors of the Electrosensory System: The NR1/NR2B N-Methyl-D-Aspartate Receptor
J Neurophysiol, February 1, 2003; 89(2): 822 - 832.
[Abstract] [Full Text] [PDF]
H. Xia, M. von Zastrow, and R. C. Malenka
A Novel Anterograde Trafficking Signal Present in the N-terminal Extracellular Domain of Ionotropic Glutamate Receptors
J. Biol. Chem., November 27, 2002; 277(49): 47765 - 47769.
[Abstract] [Full Text] [PDF]
R. Gill, A. Alanine, A. Bourson, B. Buttelmann, G. Fischer, M.-P. Heitz, J. N. C. Kew, B. Levet-Trafit, H.-P. Lorez, P. Malherbe, et al.
Pharmacological Characterization of Ro 63-1908 (1-[2-(4-Hydroxy-phenoxy)-ethyl]-4-(4-methyl-benzyl)-piperidin-4-ol), a Novel Subtype-Selective N-Methyl-D-Aspartate Antagonist
J. Pharmacol. Exp. Ther., September 1, 2002; 302(3): 940 - 948.
[Abstract] [Full Text] [PDF]
T. M. Ballard, M. Pauly-Evers, G. A. Higgins, A.-M. Ouagazzal, V. Mutel, E. Borroni, J. A. Kemp, H. Bluethmann, and J. N. C. Kew
Severe Impairment of NMDA Receptor Function in Mice Carrying Targeted Point Mutations in the Glycine Binding Site Results in Drug-Resistant Nonhabituating Hyperactivity
J. Neurosci., August 1, 2002; 22(15): 6713 - 6723.
[Abstract] [Full Text] [PDF]
W. Guo, S. Zou, Y. Guan, T. Ikeda, M. Tal, R. Dubner, and K. Ren
Tyrosine Phosphorylation of the NR2B Subunit of the NMDA Receptor in the Spinal Cord during the Development and Maintenance of Inflammatory Hyperalgesia
J. Neurosci., July 15, 2002; 22(14): 6208 - 6217.
[Abstract] [Full Text] [PDF]
K. S. Jones, H. M. A. VanDongen, and A. M. J. VanDongen
The NMDA Receptor M3 Segment Is a Conserved Transduction Element Coupling Ligand Binding to Channel Opening
J. Neurosci., March 15, 2002; 22(6): 2044 - 2053.
[Abstract] [Full Text] [PDF]
Y. Miyamoto, K. Yamada, Y. Noda, H. Mori, M. Mishina, and T. Nabeshima
Lower Sensitivity to Stress and Altered Monoaminergic Neuronal Function in Mice Lacking the NMDA Receptor epsilon 4 Subunit
J. Neurosci., March 15, 2002; 22(6): 2335 - 2342.
[Abstract] [Full Text] [PDF]
G. Woodhall, D. I. Evans, M. O. Cunningham, and R. S. G. Jones
NR2B-Containing NMDA Autoreceptors at Synapses on Entorhinal Cortical Neurons
J Neurophysiol, October 1, 2001; 86(4): 1644 - 1651.
[Abstract] [Full Text] [PDF]
J. Lerma, A. V. Paternain, A. Rodriguez-Moreno, and J. C. Lopez-Garcia
Molecular Physiology of Kainate Receptors
Physiol Rev, July 1, 2001; 81(3): 971 - 998.
[Abstract] [Full Text] [PDF]
J. N. C. Kew, A. Koester, J.-L. Moreau, F. Jenck, A.-M. Ouagazzal, V. Mutel, J. G. Richards, G. Trube, G. Fischer, A. Montkowski, et al.
Functional Consequences of Reduction in NMDA Receptor Glycine Affinity in Mice Carrying Targeted Point Mutations in the Glycine Binding Site
J. Neurosci., June 1, 2000; 20(11): 4037 - 4049.
[Abstract] [Full Text] [PDF]
B. S. Meldrum
Glutamate as a Neurotransmitter in the Brain: Review of Physiology and Pathology
J. Nutr., April 1, 2000; 130(4): 1007 - 1007.
[Abstract] [Full Text]
Z. G. Wo, K. K. Chohan, H. Chen, M. J. Sutcliffe, and R. E. Oswald
Cysteine Mutagenesis and Homology Modeling of the Ligand-binding Site of a Kainate-binding Protein
J. Biol. Chem., December 24, 1999; 274(52): 37210 - 37218.
[Abstract] [Full Text] [PDF]
A. I. Sobolevsky, S. G. Koshelev, and B. I. Khodorov
Probing of NMDA Channels with Fast Blockers
J. Neurosci., December 15, 1999; 19(24): 10611 - 10626.
[Abstract] [Full Text] [PDF]
A. Kuusinen, R. Abele, D. R. Madden, and K. Keinanen
Oligomerization and Ligand-binding Properties of the Ectodomain of the alpha -Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor Subunit GluRD
J. Biol. Chem., October 8, 1999; 274(41): 28937 - 28943.
[Abstract] [Full Text] [PDF]
L. M. Hawkins, P. L. Chazot, and F. A. Stephenson
Biochemical Evidence for the Co-association of Three N-Methyl-D-aspartate (NMDA) R2 Subunits in Recombinant NMDA Receptors
J. Biol. Chem., September 17, 1999; 274(38): 27211 - 27218.
[Abstract] [Full Text] [PDF]
J. R. Howe
REVIEW {blacksquare} : How Glutamate Receptors Are Built
Neuroscientist, September 1, 1999; 5(5): 311 - 323.
[Abstract] [PDF]
W. D. Leuschner and W. Hoch
Subtype-specific Assembly of alpha -Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor Subunits Is Mediated by Their N-terminal Domains
J. Biol. Chem., June 11, 1999; 274(24): 16907 - 16916.
[Abstract] [Full Text] [PDF]
N. W. Kleckner, J. C. Glazewski, C. C. Chen, and T. D. Moscrip
Subtype-Selective Antagonism of N-Methyl-D-Aspartate Receptors by Felbamate: Insights into the Mechanism of Action
J. Pharmacol. Exp. Ther., May 1, 1999; 289(2): 886 - 894.
[Abstract] [Full Text]
R. Dingledine, K. Borges, D. Bowie, and S. F. Traynelis
The Glutamate Receptor Ion Channels
Pharmacol. Rev., March 1, 1999; 51(1): 7 - 62.
[Abstract] [Full Text] [PDF]
R. Dunn, D Bottai, and L Maler
Molecular biology of the apteronotus NMDA receptor NR1 subunit
J. Exp. Biol., January 5, 1999; 202(10): 1319 - 1326.
[Abstract] [PDF]
W. Danysz and C. G. Parsons
Glycine and N-Methyl-D-Aspartate Receptors: Physiological Significance and Possible Therapeutic Applications
Pharmacol. Rev., December 1, 1998; 50(4): 597 - 664.
[Abstract] [Full Text] [PDF]
G. B. Wells, L. Lin, E. M. Jeanclos, and R. Anand
Assembly and Ligand Binding Properties of the Water-soluble Extracellular Domains of the Glutamate Receptor 1 Subunit
J. Biol. Chem., January 26, 2001; 276(5): 3031 - 3036.
[Abstract] [Full Text] [PDF]
E. Meddows, B. Le Bourdelles, S. Grimwood, K. Wafford, S. Sandhu, P. Whiting, and R. A. J. McIlhinney
Identification of Molecular Determinants That Are Important in the Assembly of N-Methyl-D-aspartate Receptors
J. Biol. Chem., May 25, 2001; 276(22): 18795 - 18803.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|