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. 1996 Apr 2;93(7):2741–2744. doi: 10.1073/pnas.93.7.2741

Pentameric subunit stoichiometry of a neuronal glutamate receptor.

A V Ferrer-Montiel 1, M Montal 1
PMCID: PMC39701  PMID: 8610111

Abstract

Ionotropic glutamate receptors, neurotransmitter-activated ion channels that mediate excitatory synaptic transmission in the central nervous system, are oligomeric membrane proteins of unknown subunit stoichiometry. To determine the subunit stoichiometry we have used a functional assay based on the blockade of two alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate/kainate receptor subunit 1 (GluR1) mutant subunits selectively engineered to exhibit differential sensitivity to the open channel blockers phencyclidine and dizolcipine (MK-801). Coinjection into amphibian oocytes of weakly sensitive with highly sensitive subunit complementary RNAs produces functional heteromeric channels with mixed blocker sensitivities. Increasing the fraction of the highly sensitive subunit augmented the proportion of drug-sensitive receptors. Analysis of the data using a model based on random aggregation of receptor subunits allowed us to determine a pentameric stoichiometry for GluR1. This finding supports the view that a pentameric subunit organization underlies the structure of the neuronal ionotropic glutamate receptor gene family.

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Selected References

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

  1. Bennett J. A., Dingledine R. Topology profile for a glutamate receptor: three transmembrane domains and a channel-lining reentrant membrane loop. Neuron. 1995 Feb;14(2):373–384. doi: 10.1016/0896-6273(95)90293-7. [DOI] [PubMed] [Google Scholar]
  2. Betz H. Structure and function of inhibitory glycine receptors. Q Rev Biophys. 1992 Nov;25(4):381–394. doi: 10.1017/s0033583500004340. [DOI] [PubMed] [Google Scholar]
  3. Bormann J., Hamill O. P., Sakmann B. Mechanism of anion permeation through channels gated by glycine and gamma-aminobutyric acid in mouse cultured spinal neurones. J Physiol. 1987 Apr;385:243–286. doi: 10.1113/jphysiol.1987.sp016493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Béhé P., Stern P., Wyllie D. J., Nassar M., Schoepfer R., Colquhoun D. Determination of NMDA NR1 subunit copy number in recombinant NMDA receptors. Proc Biol Sci. 1995 Nov 22;262(1364):205–213. doi: 10.1098/rspb.1995.0197. [DOI] [PubMed] [Google Scholar]
  5. Choi D. W. Bench to bedside: the glutamate connection. Science. 1992 Oct 9;258(5080):241–243. doi: 10.1126/science.1357748. [DOI] [PubMed] [Google Scholar]
  6. Collingridge G. L., Lester R. A. Excitatory amino acid receptors in the vertebrate central nervous system. Pharmacol Rev. 1989 Jun;41(2):143–210. [PubMed] [Google Scholar]
  7. Cooper E., Couturier S., Ballivet M. Pentameric structure and subunit stoichiometry of a neuronal nicotinic acetylcholine receptor. Nature. 1991 Mar 21;350(6315):235–238. doi: 10.1038/350235a0. [DOI] [PubMed] [Google Scholar]
  8. Ferrer-Montiel A. V., Sun W., Montal M. Molecular design of the N-methyl-D-aspartate receptor binding site for phencyclidine and dizolcipine. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):8021–8025. doi: 10.1073/pnas.92.17.8021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hollmann M., Heinemann S. Cloned glutamate receptors. Annu Rev Neurosci. 1994;17:31–108. doi: 10.1146/annurev.ne.17.030194.000335. [DOI] [PubMed] [Google Scholar]
  10. Hollmann M., Maron C., Heinemann S. N-glycosylation site tagging suggests a three transmembrane domain topology for the glutamate receptor GluR1. Neuron. 1994 Dec;13(6):1331–1343. doi: 10.1016/0896-6273(94)90419-7. [DOI] [PubMed] [Google Scholar]
  11. Jessell T. M., Kandel E. R. Synaptic transmission: a bidirectional and self-modifiable form of cell-cell communication. Cell. 1993 Jan;72 (Suppl):1–30. doi: 10.1016/s0092-8674(05)80025-x. [DOI] [PubMed] [Google Scholar]
  12. Langosch D., Thomas L., Betz H. Conserved quaternary structure of ligand-gated ion channels: the postsynaptic glycine receptor is a pentamer. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7394–7398. doi: 10.1073/pnas.85.19.7394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. MacKinnon R. Determination of the subunit stoichiometry of a voltage-activated potassium channel. Nature. 1991 Mar 21;350(6315):232–235. doi: 10.1038/350232a0. [DOI] [PubMed] [Google Scholar]
  14. MacKinnon R. Pore loops: an emerging theme in ion channel structure. Neuron. 1995 May;14(5):889–892. doi: 10.1016/0896-6273(95)90327-5. [DOI] [PubMed] [Google Scholar]
  15. Nakanishi S., Masu M. Molecular diversity and functions of glutamate receptors. Annu Rev Biophys Biomol Struct. 1994;23:319–348. doi: 10.1146/annurev.bb.23.060194.001535. [DOI] [PubMed] [Google Scholar]
  16. Roche K. W., Raymond L. A., Blackstone C., Huganir R. L. Transmembrane topology of the glutamate receptor subunit GluR6. J Biol Chem. 1994 Apr 22;269(16):11679–11682. [PubMed] [Google Scholar]
  17. Seeburg P. H. The TINS/TiPS Lecture. The molecular biology of mammalian glutamate receptor channels. Trends Neurosci. 1993 Sep;16(9):359–365. doi: 10.1016/0166-2236(93)90093-2. [DOI] [PubMed] [Google Scholar]
  18. Sun W., Ferrer-Montiel A. V., Schinder A. F., McPherson J. P., Evans G. A., Montal M. Molecular cloning, chromosomal mapping, and functional expression of human brain glutamate receptors. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1443–1447. doi: 10.1073/pnas.89.4.1443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Taglialatela M., Payne J. P., Drewe J. A., Brown A. M. Rescue of lethal subunits into functional K+ channels. Biophys J. 1994 Jan;66(1):179–190. doi: 10.1016/S0006-3495(94)80755-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Unwin N. Nicotinic acetylcholine receptor at 9 A resolution. J Mol Biol. 1993 Feb 20;229(4):1101–1124. doi: 10.1006/jmbi.1993.1107. [DOI] [PubMed] [Google Scholar]
  21. Villarroel A., Burnashev N., Sakmann B. Dimensions of the narrow portion of a recombinant NMDA receptor channel. Biophys J. 1995 Mar;68(3):866–875. doi: 10.1016/S0006-3495(95)80263-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wenthold R. J., Yokotani N., Doi K., Wada K. Immunochemical characterization of the non-NMDA glutamate receptor using subunit-specific antibodies. Evidence for a hetero-oligomeric structure in rat brain. J Biol Chem. 1992 Jan 5;267(1):501–507. [PubMed] [Google Scholar]
  23. Wo Z. G., Oswald R. E. Transmembrane topology of two kainate receptor subunits revealed by N-glycosylation. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7154–7158. doi: 10.1073/pnas.91.15.7154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wo Z. G., Oswald R. E. Unraveling the modular design of glutamate-gated ion channels. Trends Neurosci. 1995 Apr;18(4):161–168. doi: 10.1016/0166-2236(95)93895-5. [DOI] [PubMed] [Google Scholar]
  25. Wood M. W., VanDongen H. M., VanDongen A. M. Structural conservation of ion conduction pathways in K channels and glutamate receptors. Proc Natl Acad Sci U S A. 1995 May 23;92(11):4882–4886. doi: 10.1073/pnas.92.11.4882. [DOI] [PMC free article] [PubMed] [Google Scholar]

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