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.
Influence of a threonine residue in the S2 ligand binding domain in determining agonist potency and deactivation rate of recombinant NR1a/NR2D NMDA receptors.
???displayArticle.abstract???
NR1/NR2D NMDA receptors display unusually slow deactivation kinetics which may be critical for their role as extrasynaptic receptors. A threonine to alanine point mutation has been inserted at amino acid position 692 of the NR2D subunit (T692A). Recombinant NR1a/NR2D(T692A) NMDA receptors have been expressed in Xenopus laevis oocytes and their pharmacological and single-channel properties examined using two-electrode voltage-clamp and patch-clamp recording techniques. Glutamate dose-response curves from NR1a/NR2D(T692A) receptor channels produced an approximately 1600-fold reduction in glutamate potency compared to wild-type NR1a/NR2D receptors. There was no change in Hill slopes or gross reduction in mean maximal currents recorded in oocytes expressing either wild-type or mutant receptors. The mutation did not affect the potency of the co-agonist glycine. The shifts in potency produced by NR2D(T692A) containing receptors when activated by other glutamate-site agonists such as aspartate or NMDA were 30- to 60-fold compared to wild-type. Single-channel conductance levels of NR1a/NR2D(T692A) mutant receptors were indistinguishable from wild-type NR2D-containing channels. Additionally NR1a/NR2D(T692A) receptors showed the transitional asymmetry that is characteristic of NR2D-containing NMDA receptors. Rapid applications of glutamate on outside-out patches containing NR1a/NR2D(T692A) receptors produced macroscopic current deactivations that were about 60-fold faster than wild-type NR1a/NR2D receptors. Our results suggest that this conserved threonine residue plays a crucial role in ligand binding to NMDA NR2 receptor subunits and supports the idea that the slow decay kinetics associated with NR1a/NR2D NMDA receptors can be explained by the slow dissociation of glutamate from this NMDA receptor subtype.
Akazawa,
Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats.
1994, Pubmed
Akazawa,
Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats.
1994,
Pubmed Anson,
Identification of amino acid residues of the NR2A subunit that control glutamate potency in recombinant NR1/NR2A NMDA receptors.
1998,
Pubmed Anson,
Single-channel analysis of an NMDA receptor possessing a mutation in the region of the glutamate binding site.
2000,
Pubmed
,
Xenbase Armstrong,
Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core.
2000,
Pubmed Armstrong,
Structure of a glutamate-receptor ligand-binding core in complex with kainate.
1998,
Pubmed Banke,
Activation of NR1/NR2B NMDA receptors.
2003,
Pubmed Brickley,
NR2B and NR2D subunits coassemble in cerebellar Golgi cells to form a distinct NMDA receptor subtype restricted to extrasynaptic sites.
2003,
Pubmed Chatterton,
Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits.
2002,
Pubmed
,
Xenbase Ciabarra,
Cloning and characterization of chi-1: a developmentally regulated member of a novel class of the ionotropic glutamate receptor family.
1995,
Pubmed
,
Xenbase Clapham,
Substance P reduces acetylcholine-induced currents in isolated bovine chromaffin cells.
1984,
Pubmed Colquhoun,
Binding, gating, affinity and efficacy: the interpretation of structure-activity relationships for agonists and of the effects of mutating receptors.
1998,
Pubmed Cull-Candy,
NMDA receptor subunits: diversity, development and disease.
2001,
Pubmed Cull-Candy,
Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons.
,
Pubmed Dingledine,
The glutamate receptor ion channels.
1999,
Pubmed Furukawa,
Mechanisms of activation, inhibition and specificity: crystal structures of the NMDA receptor NR1 ligand-binding core.
2003,
Pubmed Hirai,
The glycine binding site of the N-methyl-D-aspartate receptor subunit NR1: identification of novel determinants of co-agonist potentiation in the extracellular M3-M4 loop region.
1996,
Pubmed Ishii,
Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits.
1993,
Pubmed
,
Xenbase Jin,
Structural basis for partial agonist action at ionotropic glutamate receptors.
2003,
Pubmed
,
Xenbase Jin,
Probing the function, conformational plasticity, and dimer-dimer contacts of the GluR2 ligand-binding core: studies of 5-substituted willardiines and GluR2 S1S2 in the crystal.
2003,
Pubmed Keinänen,
Characterization of the kainate-binding domain of the glutamate receptor GluR-6 subunit.
1998,
Pubmed Kuner,
Multiple structural elements determine subunit specificity of Mg2+ block in NMDA receptor channels.
1996,
Pubmed
,
Xenbase Kuryatov,
Mutational analysis of the glycine-binding site of the NMDA receptor: structural similarity with bacterial amino acid-binding proteins.
1994,
Pubmed
,
Xenbase Kutsuwada,
Molecular diversity of the NMDA receptor channel.
1992,
Pubmed
,
Xenbase Kuusinen,
Molecular dissection of the agonist binding site of an AMPA receptor.
1995,
Pubmed Lampinen,
AMPA receptors and bacterial periplasmic amino acid-binding proteins share the ionic mechanism of ligand recognition.
1998,
Pubmed Laube,
Molecular determinants of agonist discrimination by NMDA receptor subunits: analysis of the glutamate binding site on the NR2B subunit.
1997,
Pubmed Lester,
NMDA channel behavior depends on agonist affinity.
1992,
Pubmed Magleby,
Burst kinetics of single calcium-activated potassium channels in cultured rat muscle.
1983,
Pubmed Misra,
Slow deactivation kinetics of NMDA receptors containing NR1 and NR2D subunits in rat cerebellar Purkinje cells.
2000,
Pubmed Momiyama,
Distinct synaptic and extrasynaptic NMDA receptors identified in dorsal horn neurones of the adult rat spinal cord.
2000,
Pubmed Monyer,
Heteromeric NMDA receptors: molecular and functional distinction of subtypes.
1992,
Pubmed Monyer,
Developmental and regional expression in the rat brain and functional properties of four NMDA receptors.
1994,
Pubmed Paas,
Identification of the amino acid subsets accounting for the ligand binding specificity of a glutamate receptor.
1996,
Pubmed Popescu,
Modal gating of NMDA receptors and the shape of their synaptic response.
2003,
Pubmed Stern,
Single-channel conductances of NMDA receptors expressed from cloned cDNAs: comparison with native receptors.
1992,
Pubmed
,
Xenbase Stern-Bach,
Agonist selectivity of glutamate receptors is specified by two domains structurally related to bacterial amino acid-binding proteins.
1994,
Pubmed
,
Xenbase Sucher,
Developmental and regional expression pattern of a novel NMDA receptor-like subunit (NMDAR-L) in the rodent brain.
1995,
Pubmed
,
Xenbase Sugihara,
Structures and properties of seven isoforms of the NMDA receptor generated by alternative splicing.
1992,
Pubmed
,
Xenbase Vicini,
Functional and pharmacological differences between recombinant N-methyl-D-aspartate receptors.
1998,
Pubmed Watanabe,
Developmental changes in distribution of NMDA receptor channel subunit mRNAs.
1992,
Pubmed Wo,
Cysteine mutagenesis and homology modeling of the ligand-binding site of a kainate-binding protein.
1999,
Pubmed Wyllie,
Single-channel currents from recombinant NMDA NR1a/NR2D receptors expressed in Xenopus oocytes.
1996,
Pubmed
,
Xenbase Wyllie,
Single-channel activations and concentration jumps: comparison of recombinant NR1a/NR2A and NR1a/NR2D NMDA receptors.
1998,
Pubmed
,
Xenbase
