Primary structure and expression of the γ2 subunit of the glutamate receptor channel selective for kainate

doi:10.1016/0896-6273(92)90293-M

Neuron

Volume 8, Issue 2, February 1992, Pages 267-274

https://doi.org/10.1016/0896-6273(92)90293-M Get rights and content

Abstract

The presence and primary structure of a novel subunit of the mouse glutamate receptor channel, designated as γ2, have been revealed by cloning and sequencing the cDNA. The γ2 subunit has structural characteristics common to the neurotransmitter-gated ion channel family and shares a high amino acid sequence identity with the rat KA-1 subunit, thus constituting the γ subfamily of the glutamate receptor channel. Expression of the γ2 subunit together with the β2 subunit in Xenopus oocytes yields functional glutamate receptor channels selective for kainate.

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In this study, we used seven NMDA-NR2A−/− mutant mice and ten of their wild type littermates for electrophysiological recordings and eight NMDA-NR2A−/− mutant mice and nine of their wild type littermates for behavioural studies (Sakimura et al., 1992).
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They bind kainate with high affinity and form functional channels activated by glutamate and kainate which are enhanced in the presence of concanavalin A (Hollmann and Heinemann, 1994; Nakanishi and Masu, 1994; Sprengel and Seeburg, 1993). A subunit with even higher kainate affinity, KA1, was cloned by Werner et al. (1991); this was followed by the cloning of a second one variously named KA2 in the rat (Herb et al., 1992) and γ in the mouse (Sakimura et al., 1992). The equivalents in man were named as humEAA1 and humEAA2 (Kamboj et al., 1992, 1994).
In this article, the beginnings of glutamate pharmacology are traced from the early doubts about ‘non-specific’ excitatory effects, through glutamate- and aspartate-preferring receptors, to NMDA, quisqualate/AMPA and kainate subtypes, and finally to the cloning of genes for these receptor subunits. The development of selective antagonists, crucial to the subtype classification, allowed the fundamental importance of glutamate receptors to synaptic activity throughout the CNS to be realised. The ability to be able to express and manipulate cloned receptor subunits is leading to huge advances in our understanding of these receptors. Similarly the tortuous path of the nomenclature is followed from naming with reference to exogenous agonists, through abortive early attempts at generic schemes, and back to the NC-IUPHAR system based on the natural agonist, the defining exogenous agonist and the gene names.

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Neuron

ArticlePrimary structure and expression of the γ2 subunit of the glutamate receptor channel selective for kainate

Abstract

Trends Neurosci.

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Trends Neurosci.

Neuron

Cell

Prog. Neurobiol.

Brain Res. Rev.

Biochem. Biophys. Res. Commun.

Neuron

J. Biol. Chem.

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FEBS Lett.

Neuroscience

Brain Res.

Brain Res.

FEBS Lett.

Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose

Proc. Natl. Acad. Sci. USA

Molecular cloning and functional expression of glutamate receptor subunit genes

Science

Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

Biochemistry

The nicotinic cholinergic receptor: correlation of molecular structure with functional properties

Annu. Rev. Biochem.

Amino acid sequences surrounding the CAMP-dependent and calcium/ calmodulin-dependent phosphorylation sites in rat and bovine synapsin l

Protein serine/threonine kinases

Annu. Rev. Biochem.

Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA

Nature

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Primary structure and expression of the γ₂ subunit of the glutamate receptor channel selective for kainate