Molecular cloning, chromosomal mapping, and functional expression of human brain glutamate receptors

William Sun, Antonio V. Ferrer-Montiel, Alejandro F. Schinder, John P. Mcpherson, Glen A. Evans, Mauricio Montal

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

A full-length cDNA clone encoding a glutamate receptor was isolated from a human brain cDNA library, and the gene product was characterized after expression in Xenopus oocytes. Degenerate PCR primers to conserved regions of published rat brain glutamate receptor sequences amplified a 1-kilobase fragment from a human brain cDNA library. This fragment was used as a probe for subsequent hybridization screening. Two clones were isolated that, based on sequence information, code for different receptors: a 3-kilobase clone, HBGR1, contains a full-length glutamate receptor cDNA highly homologous to the rat brain clone GluR1, and a second clone, HBGR2, contains approximately two-thirds of the coding region of a receptor homologous to rat brain clone GluR2. Southern and PCR analysis of a somatic cell-hybrid panel mapped HBGR1 to human chromosome 5q31.3-33.3 and mapped HBGR2 to chromosome 4q25-34.3. Xenopus oocytes injected with in vitro-synthesized HBGR1 cRNA expressed currents activated by glutamate receptor agonists with the following specificity sequence: domoate > kainate >> quisqualate ≥ α-amino-3-hydroxy-5-methy)-4-isoxazole propionic acid ≥ L-glutamate >> N-methyl-D-aspartate. The kainate-elicited currents were specifically blocked by 6-cyano-7-nitroquinoxaline-2,3-dione but were insensitive to 2-amino-5-phosphonovalerate and kynurenic acid. These results indicate that clone HBGR1 codes for a glutamate receptor of the kainate subtype cognate to members of the glutamate receptor family from rodent brain.

Original languageEnglish (US)
Pages (from-to)1443-1447
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number4
DOIs
StatePublished - Feb 15 1992
Externally publishedYes

Keywords

  • Human genome
  • Ionic channels
  • Membrane receptors
  • N-methyl-D-aspartate receptors
  • Neurotoxicity

ASJC Scopus subject areas

  • General

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