Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Nov 1;89(21):10484–10488. doi: 10.1073/pnas.89.21.10484

Glutamate receptors of Drosophila melanogaster: cloning of a kainate-selective subunit expressed in the central nervous system.

A Ultsch 1, C M Schuster 1, B Laube 1, P Schloss 1, B Schmitt 1, H Betz 1
PMCID: PMC50363  PMID: 1359540

Abstract

We report the isolation and functional characterization of cDNAs encoding a Drosophila kainate-selective glutamate receptor. The deduced mature 964-residue protein (DGluR-I) is 108,482 Da and exhibits significant homology to mammalian glutamate receptor subunits. Injection of DGluR-I cRNA into Xenopus oocytes generated kainate-operated ion channels which were blocked by the selective non-N-methyl-D-aspartate receptor antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione and philanthotoxin. DGluR-I transcripts are differentially expressed during Drosophila development and, in late embryogenesis, accumulate in the central nervous system.

Full text

PDF

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Betz H. Ligand-gated ion channels in the brain: the amino acid receptor superfamily. Neuron. 1990 Oct;5(4):383–392. doi: 10.1016/0896-6273(90)90077-s. [DOI] [PubMed] [Google Scholar]
  2. Blair L. A., Levitan E. S., Marshall J., Dionne V. E., Barnard E. A. Single subunits of the GABAA receptor form ion channels with properties of the native receptor. Science. 1988 Oct 28;242(4878):577–579. doi: 10.1126/science.2845583. [DOI] [PubMed] [Google Scholar]
  3. Bolshakov VYu, Gapon S. A., Magazanik L. G. Different types of glutamate receptors in isolated and identified neurones of the mollusc Planorbarius corneus. J Physiol. 1991 Aug;439:15–35. doi: 10.1113/jphysiol.1991.sp018654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cull-Candy S. G. Two types of extrajunctional L-glutamate receptors in locust muscle fibres. J Physiol. 1976 Feb;255(2):449–464. doi: 10.1113/jphysiol.1976.sp011289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Egebjerg J., Bettler B., Hermans-Borgmeyer I., Heinemann S. Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA. Nature. 1991 Jun 27;351(6329):745–748. doi: 10.1038/351745a0. [DOI] [PubMed] [Google Scholar]
  6. Fraser S. P., Djamgoz M. B., Usherwood P. N., O'Brien J., Darlison M. G., Barnard E. A. Amino acid receptors from insect muscle: electrophysiological characterization in Xenopus oocytes following expression by injection of mRNA. Brain Res Mol Brain Res. 1990 Oct;8(4):331–341. doi: 10.1016/0169-328x(90)90047-h. [DOI] [PubMed] [Google Scholar]
  7. Giles D., Usherwood P. N. The effects of putative amino acid neurotransmitters on somata isolated from neurons of the locust central nervous system. Comp Biochem Physiol C. 1985;80(2):231–236. doi: 10.1016/0742-8413(85)90047-7. [DOI] [PubMed] [Google Scholar]
  8. Harvey R. J., Vreugdenhil E., Zaman S. H., Bhandal N. S., Usherwood P. N., Barnard E. A., Darlison M. G. Sequence of a functional invertebrate GABAA receptor subunit which can form a chimeric receptor with a vertebrate alpha subunit. EMBO J. 1991 Nov;10(11):3239–3245. doi: 10.1002/j.1460-2075.1991.tb04887.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hermans-Borgmeyer I., Zopf D., Ryseck R. P., Hovemann B., Betz H., Gundelfinger E. D. Primary structure of a developmentally regulated nicotinic acetylcholine receptor protein from Drosophila. EMBO J. 1986 Jul;5(7):1503–1508. doi: 10.1002/j.1460-2075.1986.tb04389.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hollmann M., O'Shea-Greenfield A., Rogers S. W., Heinemann S. Cloning by functional expression of a member of the glutamate receptor family. Nature. 1989 Dec 7;342(6250):643–648. doi: 10.1038/342643a0. [DOI] [PubMed] [Google Scholar]
  11. Horseman B. G., Seymour C., Bermudez I., Beadle D. J. The effects of L-glutamate on cultured insect neurones. Neurosci Lett. 1988 Feb 15;85(1):65–70. doi: 10.1016/0304-3940(88)90430-2. [DOI] [PubMed] [Google Scholar]
  12. Hutton M. L., Harvey R. J., Barnard E. A., Darlison M. G. Cloning of a cDNA that encodes an invertebrate glutamate receptor subunit. FEBS Lett. 1991 Nov 4;292(1-2):111–114. doi: 10.1016/0014-5793(91)80846-u. [DOI] [PubMed] [Google Scholar]
  13. Jan L. Y., Jan Y. N. L-glutamate as an excitatory transmitter at the Drosophila larval neuromuscular junction. J Physiol. 1976 Oct;262(1):215–236. doi: 10.1113/jphysiol.1976.sp011593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kawai N., Saito M., Ohsako S. Differential expression of glutamate receptors in Xenopus oocytes injected with messenger RNA from lobster muscle. Neurosci Lett. 1988 Dec 19;95(1-3):203–207. doi: 10.1016/0304-3940(88)90657-x. [DOI] [PubMed] [Google Scholar]
  15. Keinänen K., Wisden W., Sommer B., Werner P., Herb A., Verdoorn T. A., Sakmann B., Seeburg P. H. A family of AMPA-selective glutamate receptors. Science. 1990 Aug 3;249(4968):556–560. doi: 10.1126/science.2166337. [DOI] [PubMed] [Google Scholar]
  16. Kennedy M. B. Regulation of synaptic transmission in the central nervous system: long-term potentiation. Cell. 1989 Dec 1;59(5):777–787. doi: 10.1016/0092-8674(89)90601-6. [DOI] [PubMed] [Google Scholar]
  17. Kornfeld K., Saint R. B., Beachy P. A., Harte P. J., Peattie D. A., Hogness D. S. Structure and expression of a family of Ultrabithorax mRNAs generated by alternative splicing and polyadenylation in Drosophila. Genes Dev. 1989 Feb;3(2):243–258. doi: 10.1101/gad.3.2.243. [DOI] [PubMed] [Google Scholar]
  18. Marshall J., Buckingham S. D., Shingai R., Lunt G. G., Goosey M. W., Darlison M. G., Sattelle D. B., Barnard E. A. Sequence and functional expression of a single alpha subunit of an insect nicotinic acetylcholine receptor. EMBO J. 1990 Dec;9(13):4391–4398. doi: 10.1002/j.1460-2075.1990.tb07889.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Monaghan D. T., Bridges R. J., Cotman C. W. The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system. Annu Rev Pharmacol Toxicol. 1989;29:365–402. doi: 10.1146/annurev.pa.29.040189.002053. [DOI] [PubMed] [Google Scholar]
  20. Moriyoshi K., Masu M., Ishii T., Shigemoto R., Mizuno N., Nakanishi S. Molecular cloning and characterization of the rat NMDA receptor. Nature. 1991 Nov 7;354(6348):31–37. doi: 10.1038/354031a0. [DOI] [PubMed] [Google Scholar]
  21. Needleman S. B., Wunsch C. D. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol. 1970 Mar;48(3):443–453. doi: 10.1016/0022-2836(70)90057-4. [DOI] [PubMed] [Google Scholar]
  22. Olney J. W. Excitotoxic amino acids and neuropsychiatric disorders. Annu Rev Pharmacol Toxicol. 1990;30:47–71. doi: 10.1146/annurev.pa.30.040190.000403. [DOI] [PubMed] [Google Scholar]
  23. Patlak J. B., Gration K. A., Usherwood P. N. Single glutamate-activated channels in locust muscle. Nature. 1979 Apr 12;278(5705):643–645. doi: 10.1038/278643a0. [DOI] [PubMed] [Google Scholar]
  24. Sansom M. S., Usherwood P. N. Single-channel studies of glutamate receptors. Int Rev Neurobiol. 1990;32:51–106. doi: 10.1016/s0074-7742(08)60580-2. [DOI] [PubMed] [Google Scholar]
  25. Sawruk E., Schloss P., Betz H., Schmitt B. Heterogeneity of Drosophila nicotinic acetylcholine receptors: SAD, a novel developmentally regulated alpha-subunit. EMBO J. 1990 Sep;9(9):2671–2677. doi: 10.1002/j.1460-2075.1990.tb07452.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sawruk E., Udri C., Betz H., Schmitt B. SBD, a novel structural subunit of the Drosophila nicotinic acetylcholine receptor, shares its genomic localization with two alpha-subunits. FEBS Lett. 1990 Oct 29;273(1-2):177–181. doi: 10.1016/0014-5793(90)81078-3. [DOI] [PubMed] [Google Scholar]
  27. Schmieden V., Grenningloh G., Schofield P. R., Betz H. Functional expression in Xenopus oocytes of the strychnine binding 48 kd subunit of the glycine receptor. EMBO J. 1989 Mar;8(3):695–700. doi: 10.1002/j.1460-2075.1989.tb03428.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schuster C. M., Ultsch A., Schloss P., Cox J. A., Schmitt B., Betz H. Molecular cloning of an invertebrate glutamate receptor subunit expressed in Drosophila muscle. Science. 1991 Oct 4;254(5028):112–114. doi: 10.1126/science.1681587. [DOI] [PubMed] [Google Scholar]
  29. Sommer B., Keinänen K., Verdoorn T. A., Wisden W., Burnashev N., Herb A., Köhler M., Takagi T., Sakmann B., Seeburg P. H. Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS. Science. 1990 Sep 28;249(4976):1580–1585. doi: 10.1126/science.1699275. [DOI] [PubMed] [Google Scholar]
  30. Sommer B., Seeburg P. H. Glutamate receptor channels: novel properties and new clones. Trends Pharmacol Sci. 1992 Jul;13(7):291–296. doi: 10.1016/0165-6147(92)90088-n. [DOI] [PubMed] [Google Scholar]
  31. Tautz D., Pfeifle C. A non-radioactive in situ hybridization method for the localization of specific RNAs in Drosophila embryos reveals translational control of the segmentation gene hunchback. Chromosoma. 1989 Aug;98(2):81–85. doi: 10.1007/BF00291041. [DOI] [PubMed] [Google Scholar]
  32. Watkins J. C., Krogsgaard-Larsen P., Honoré T. Structure-activity relationships in the development of excitatory amino acid receptor agonists and competitive antagonists. Trends Pharmacol Sci. 1990 Jan;11(1):25–33. doi: 10.1016/0165-6147(90)90038-a. [DOI] [PubMed] [Google Scholar]
  33. Werner P., Voigt M., Keinänen K., Wisden W., Seeburg P. H. Cloning of a putative high-affinity kainate receptor expressed predominantly in hippocampal CA3 cells. Nature. 1991 Jun 27;351(6329):742–744. doi: 10.1038/351742a0. [DOI] [PubMed] [Google Scholar]
  34. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES