N-methyl-d-aspartate receptors (NMDARs) play an important role in many aspects of nervous system function such as synaptic plasticity and neuronal development. NMDARs are heteromers consisting of an obligate NR1 and most commonly one or two kinds of NR2 subunits. While the receptors have been well characterized in some vertebrate and invertebrate systems, information about NMDARs in Xenopus laevis brain is incomplete. Here we provide biochemical evidence that the NR1, NR2A and NR2B subunits of NMDARs are expressed in the central nervous system of X. laevis tadpoles. The NR1-4a/b splice variants appear to be the predominant isoforms while the NR1-3a/b variants appear to be expressed at low levels. We cloned the X. laevis NR2A and NR2B subunits and provide a detailed annotation of their functional domains in comparison with NR2A and NR2B proteins from 10 and 13 other species, respectively. Both NR2A and NR2B proteins are remarkably well conserved between species, consistent with the importance of NMDARs in nervous system function

Cline, Hollis T.

Ewald, Rebecca C.

English

PubMed

N-methyl-D-aspartate receptors (NMDARs) play an important role in many aspects of nervous system function such as synaptic plasticity and neuronal development. NMDARs are heteromers consisting of an obligate NR1 and most commonly one or two kinds of NR2 subunits. While the receptors have been well characterized in some vertebrate and invertebrate systems, information about NMDARs in Xenopus laevis brain is incomplete. Here we provide biochemical evidence that the NR1, NR2A and NR2B subunits of NMDARs are expressed in the central nervous system of X. laevis tadpoles. The NR1-4a/b splice variants appear to be the predominant isoforms while the NR1-3a/b variants appear to be expressed at low levels. We cloned the X. laevis NR2A and NR2B subunits and provide a detailed annotation of their functional domains in comparison with NR2A and NR2B proteins from 10 and 13 other species, respectively. Both NR2A and NR2B proteins are remarkably well conserved between species, consistent with the importance of NMDARs in nervous system function

Rebecca  C  Ewald

Hollis Cline

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Frontiers in Molecular Neuroscience

Cloning and phylogenetic analysis of NMDA receptor subunits NR1, NR2A and NR2B in Xenopus laevis tadpoles

Ewald,  R. C.

Cline,  H. T.

Cold Spring Harbor Laboratory Institutional Repository

Cloning and Phylogenetic Analysis of NMDA Receptor Subunits NR1, NR2A and NR2B in Xenopus laevis Tadpoles

A common architecture for K+ channels and ionotropic glutamate receptors?

A usedependent tyrosine dephosphorylation of NMDA receptors is independent of ion ﬂ ux.

Activity-dependent mRNA splicing controls ER export and synaptic delivery of NMDA receptors.

Adjacent asparagines in the NR2-subunit of the NMDA receptor channel control the voltage-dependent block by extracellular Mg2+.

Alternative RNA splicing of the NMDA receptor NR1 mRNA in the neurons of the teleost electrosensory system.

Alternatively spliced isoforms of the NMDARI receptor subunit.

Apparent homomeric NR1 currents observed in Xenopus oocytes are caused by an endogenous NR2 subunit.

Characterization of Fyn-mediated tyrosine phosphorylation sites on GluR epsilon 2 (NR2B) subunit of the N-methyl-D-aspartate receptor.

Cloning and characterization of the chick NMDA receptor subunit-1 gene. Brain Res.

Cloning and phylogenetic analysis of NMDA receptor subunits NR1, NR2A and NR2B in Xenopus laevis tadpoles.

Cloning and sequence analysis of additional splice variants encoding human N-methylD-aspartate receptor (hNR1) subunits.

Cloning and sequence analysis of cDNAs encoding human hippocampus N-methyl-Daspartate receptor subunits: evidence for alternative RNA splicing.

Cloning of an apparent splice variant of the rat N-methyl-D-aspartate receptor NMDAR1 with altered sensitivity to Frontiers

Control of proton sensitivity of the NMDA receptor by RNA splicing and polyamines.

Control of voltage- independent zinc inhibition of NMDA receptors Frontiers in Molecular Neuroscience www.frontiersin.org

Dendrite growth increased by visual activity requires NMDA receptor and Rho GTPases.

Developmental and regional expression in the rat brain and functional properties of four NMDA receptors.

Developmental expression of N-methyl-D-aspartate glutamate receptor 1 splice variants in the chick retina.

Developmental regulation of CPG15 expression in Xenopus.

Differential binding of the AP-2 adaptor complex and PSD-95 to the C- terminus of the NMDA receptor subunit NR2B regulates surface expression.

Differential contribution of the NR1- and NR2Asubunits to the selectivity filter of recombinant NMDA receptor channels.

Endocytosis and degradative sorting of NMDA receptors by conserved membrane-proximal signals.

Enhanced visual activity in vivo forms nascent synapses in the developing retinotectal projection.

Evidence for direct protein kinase-C mediated modulation of N-methyl-D-aspartate receptor current.

Four residues of the extracellular N-terminal domain of the NR2A subunit control high-afﬁ nity Zn2+ binding to NMDA receptors.

Functional and pharmacological differences between recombinant N-methyl-Daspartate receptors.

Functional expression of a recombinant unitary glutamate receptor from Xenopus, which contains N-methyl-D-aspartate (NMDA) and non-NMDA receptor subunits.

Glutamate receptor function in learning and memory.

Identiﬁ cation of a phosphorylation site for calcium/calmodulindependent protein kinase II in the NR2B subunit of the N-methyl-D-aspartate receptor.

Identiﬁ cation of amino acid residues of the NR2A subunit that control glutamate potency in recombinant NR1/NR2A NMDA receptors.

Identiﬁ cation of two NOGO/ RTN4 genes and analysis of Nogo-A expression in Xenopus laevis.

In vivo development of neuronal structure and function.

Ligandgated ion channel interactions with cytoskeletal and signaling proteins.

Mapping the binding site of the neuroprotectant ifenprodil on NMDA receptors.

Mechanism and regulation of calcium/calmodulin-dependent protein kinase II targeting to the NR2B subunit of the N-methyl-Daspartate receptor.

Molecular characterization and embryonic expression of the family of N-methyl-D-aspartate receptor subunit genes in the zebraﬁ sh.

Molecular cloning and characterization of the rat NMDA receptor.

Molecular determinants of agonist discrimination by NMDA receptor subunits: analysis of the glutamate binding site on the NR2B subunit.

Molecular determinants of NMDA receptor internalization.

Molecular organization of a zinc binding n-terminal modulatory domain in a NMDA receptor subunit.

Mutagenesis rescues spermine and Zn2+ potentiation of recombinant NMDA receptors.

N- terminal domains in the NR2 subunit control desensitization of NMDA receptors.

N-methyl-D-aspartate receptor subtypes: multiple roles in excitotoxicity and neurological disease.

Neural activity and the dynamics of central nervous system development.

NMDA receptor subunits: diversity, development and disease.

NMDA receptors mediate olfactory learning and memory in Drosophila.

paper pending published: 14

PDZ domain suppression of an ER retention signal in NMDA receptor NR1 splice variants.

PKC site mutations reveal differential modulation by insulin of NMDA receptors containing NR2A or NR2B subunits.

Promotion of dendritic growth by CPG15, an activityinduced signaling molecule.

Protein kinase C activation modulates alphacalmodulin kinase II binding to NR2A subunit of N-methyl-D-aspartate receptor complex.

Regional and developmental heterogeneity in splicing of the rat brain NMDAR1 mRNA.

Regional, developmental and interspecies expression of the four NMDAR2 subunits, examined using monoclonal antibodies. Brain Res.

Regulated subcellular distribution of the NR1 subunit of the NMDA receptor.

Revisiting the postulated “unitary glutamate receptor”: electrophysiological and pharmacological analysis in two heterologous expression systems fails to detect evidence for its existence.

Role of distinct NMDA receptor subtypes at central synapses.

Roles of NR2A and NR2B in the development of dendritic arbor morphology in vivo.

Sequence determinants on the NR2A and NR2B subunits of NMDA receptor responsible for speciﬁ city of phosphorylation by CaMKII.

Spermine potentiation of recombinant Nmethyl-D-aspartate receptors is affected by subunit composition.

Splice variants of the N-methyl-D-aspartate receptor NR1 identify domains involved in regulation by polyamines and protein kinase C.

Structural features of the glutamate binding site in recombinant NR1/NR2A N-methylD-aspartate receptors determined by site-directed mutagenesis and molecular modeling.

Structure of the NMDA receptor channel M2 segment inferred from the accessibility of substituted cysteines.

Structures and properties of seven isoforms of the NMDA receptor generated by alternative splicing.

Subunit-specific NMDA receptor trafficking to synapses.

Subunitspeciﬁ c regulation of NMDA receptor endocytosis.

The C. elegans glutamate receptor subunit NMR-1 is required for slow NMDA-activated currents that regulate reversal frequency during locomotion.

The glutamate receptor ion channels.

The N-methyl-D-aspartate receptor splice variant NR1-4 C-terminal domain. Deletion analysis and role in subcellular distribution.

The synaptic localization of NR2B-containing NMDA receptors is controlled by interactions with PDZ proteins and AP-2.

Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc inhibition.

Uncoupling dendrite growth and patterning: single-cell knockout analysis of NMDA receptor 2B.

Zinc potentiates agonist-induced currents at certain splice variants of the NMDA receptor.

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Cloning and Phylogenetic Analysis of NMDA Receptor Subunits NR1, NR2A and NR2B in Xenopus laevis Tadpoles

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