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EMBO J. 1990 Mar; 9(3): 771–776.
doi: 10.1002/j.1460-2075.1990.tb08172.x
PMCID: PMC551735
PMID: 2155780

Alpha subunit variants of the human glycine receptor: primary structures, functional expression and chromosomal localization of the corresponding genes.

G Grenningloh, V Schmieden, P R Schofield, P H Seeburg, T Siddique, T K Mohandas, C M Becker, and H Betz
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Abstract

Two cDNAs encoding variants (alpha 1 and alpha 2) of the strychnine binding subunit of the inhibitory glycine receptor (GlyR) were isolated from a human fetal brain cDNA library. The predicted amino acid sequences exhibit approximately 99% and approximately 76% identity to the previously characterized rat 48 kd polypeptide. Heterologous expression of the human alpha 1 and alpha 2 subunits in Xenopus oocytes resulted in the formation of glycine-gated strychnine-sensitive chloride channels, indicating that both polypeptides can form functional GlyRs. Using a panel of rodent-human hybrid cell lines, the gene encoding alpha 2 was mapped to the short arm (Xp21.2-p22.1) of the human X chromosome. In contrast, the alpha 1 subunit gene is autosomally located. These data indicate molecular heterogeneity of the human GlyR at the level of alpha subunit genes.

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Selected References

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  • Andermann F, Keene DL, Andermann E, Quesney LF. Startle disease or hyperekplexia: further delineation of the syndrome. Brain. 1980 Dec;103(4):985–997. [PubMed] [Google Scholar]
  • Akagi H, Miledi R. Heterogeneity of glycine receptors and their messenger RNAs in rat brain and spinal cord. Science. 1988 Oct 14;242(4876):270–273. [PubMed] [Google Scholar]
  • Barker JL, McBurney RN. GABA and glycine may share the same conductance channel on cultured mammalian neurones. Nature. 1979 Jan 18;277(5693):234–236. [PubMed] [Google Scholar]
  • Becker CM, Hoch W, Betz H. Glycine receptor heterogeneity in rat spinal cord during postnatal development. EMBO J. 1988 Dec 1;7(12):3717–3726. [PMC free article] [PubMed] [Google Scholar]
  • Bormann J, Hamill OP, 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. [PMC free article] [PubMed] [Google Scholar]
  • Deneris ES, Connolly J, Boulter J, Wada E, Wada K, Swanson LW, Patrick J, Heinemann S. Primary structure and expression of beta 2: a novel subunit of neuronal nicotinic acetylcholine receptors. Neuron. 1988 Mar;1(1):45–54. [PubMed] [Google Scholar]
  • Eicher EM, Lane PW. Assignment of LH XVI to chromosome 3 in the mouse. J Hered. 1980 Sep-Oct;71(5):315–318. [PubMed] [Google Scholar]
  • Gorman CM, Gies D, McCray G, Huang M. The human cytomegalovirus major immediate early promoter can be trans-activated by adenovirus early proteins. Virology. 1989 Aug;171(2):377–385. [PubMed] [Google Scholar]
  • Grenningloh G, Rienitz A, Schmitt B, Methfessel C, Zensen M, Beyreuther K, Gundelfinger ED, Betz H. The strychnine-binding subunit of the glycine receptor shows homology with nicotinic acetylcholine receptors. Nature. 1987 Jul 16;328(6127):215–220. [PubMed] [Google Scholar]
  • Grenningloh G, Gundelfinger E, Schmitt B, Betz H, Darlison MG, Barnard EA, Schofield PR, Seeburg PH. Glycine vs GABA receptors. Nature. 1987 Nov 5;330(6143):25–26. [PubMed] [Google Scholar]
  • Gundlach AL, Dodd PR, Grabara CS, Watson WE, Johnston GA, Harper PA, Dennis JA, Healy PJ. Deficit of spinal cord glycine/strychnine receptors in inherited myoclonus of Poll Hereford calves. Science. 1988 Sep 30;241(4874):1807–1810. [PubMed] [Google Scholar]
  • Hamill OP, Bormann J, Sakmann B. Activation of multiple-conductance state chloride channels in spinal neurones by glycine and GABA. Nature. 305(5937):805–808. [PubMed] [Google Scholar]
  • Harding AE. Hereditary "pure" spastic paraplegia: a clinical and genetic study of 22 families. J Neurol Neurosurg Psychiatry. 1981 Oct;44(10):871–883. [PMC free article] [PubMed] [Google Scholar]
  • Hoch W, Betz H, Becker CM. Primary cultures of mouse spinal cord express the neonatal isoform of the inhibitory glycine receptor. Neuron. 1989 Sep;3(3):339–348. [PubMed] [Google Scholar]
  • Levitan ES, Schofield PR, Burt DR, Rhee LM, Wisden W, Köhler M, Fujita N, Rodriguez HF, Stephenson A, Darlison MG, et al. Structural and functional basis for GABAA receptor heterogeneity. Nature. 1988 Sep 1;335(6185):76–79. [PubMed] [Google Scholar]
  • Martin JB. Molecular genetic studies in the neuropsychiatric disorders. Trends Neurosci. 1989 Apr;12(4):130–137. [PubMed] [Google Scholar]
  • Nadeau JH. Maps of linkage and synteny homologies between mouse and man. Trends Genet. 1989 Mar;5(3):82–86. [PubMed] [Google Scholar]
  • Nef P, Oneyser C, Alliod C, Couturier S, Ballivet M. Genes expressed in the brain define three distinct neuronal nicotinic acetylcholine receptors. EMBO J. 1988 Mar;7(3):595–601. [PMC free article] [PubMed] [Google Scholar]
  • Pfeiffer F, Graham D, Betz H. Purification by affinity chromatography of the glycine receptor of rat spinal cord. J Biol Chem. 1982 Aug 25;257(16):9389–9393. [PubMed] [Google Scholar]
  • Pfeiffer F, Simler R, Grenningloh G, Betz H. Monoclonal antibodies and peptide mapping reveal structural similarities between the subunits of the glycine receptor of rat spinal cord. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7224–7227. [PMC free article] [PubMed] [Google Scholar]
  • Pritchett DB, Sontheimer H, Gorman CM, Kettenmann H, Seeburg PH, Schofield PR. Transient expression shows ligand gating and allosteric potentiation of GABAA receptor subunits. Science. 1988 Dec 2;242(4883):1306–1308. [PubMed] [Google Scholar]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed] [Google Scholar]
  • Schmieden V, Grenningloh G, Schofield PR, 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. [PMC free article] [PubMed] [Google Scholar]
  • Schofield PR, Darlison MG, Fujita N, Burt DR, Stephenson FA, Rodriguez H, Rhee LM, Ramachandran J, Reale V, Glencorse TA, et al. Sequence and functional expression of the GABA A receptor shows a ligand-gated receptor super-family. Nature. 1987 Jul 16;328(6127):221–227. [PubMed] [Google Scholar]
  • Schofield PR, Pritchett DB, Sontheimer H, Kettenmann H, Seeburg PH. Sequence and expression of human GABAA receptor alpha 1 and beta 1 subunits. FEBS Lett. 1989 Feb 27;244(2):361–364. [PubMed] [Google Scholar]
  • Siddique T, McKinney R, Hung WY, Bartlett RJ, Bruns G, Mohandas TK, Ropers HH, Wilfert C, Roses AD. The poliovirus sensitivity (PVS) gene is on chromosome 19q12----q13.2. Genomics. 1988 Aug;3(2):156–160. [PubMed] [Google Scholar]
  • Siddique T, Phillips K, Betz H, Grenningloh G, Warner K, Hung WY, Laing N, Roses AD. RFLPs of the gene for the human glycine receptor on the X-chromosome. Nucleic Acids Res. 1989 Feb 25;17(4):1785–1785. [PMC free article] [PubMed] [Google Scholar]
  • Sigel E, Barnard EA. A gamma-aminobutyric acid/benzodiazepine receptor complex from bovine cerebral cortex. Improved purification with preservation of regulatory sites and their interactions. J Biol Chem. 1984 Jun 10;259(11):7219–7223. [PubMed] [Google Scholar]
  • Sontheimer H, Becker CM, Pritchett DB, Schofield PR, Grenningloh G, Kettenmann H, Betz H, Seeburg PH. Functional chloride channels by mammalian cell expression of rat glycine receptor subunit. Neuron. 1989 May;2(5):1491–1497. [PubMed] [Google Scholar]
  • Thakker RV, Read AP, Davies KE, Whyte MP, Weksberg R, Glorieux F, Davies M, Mountford RC, Harris R, King A, et al. Bridging markers defining the map position of X linked hypophosphataemic rickets. J Med Genet. 1987 Dec;24(12):756–760. [PMC free article] [PubMed] [Google Scholar]
  • White WF, Heller AH. Glycine receptor alteration in the mutant mouse spastic. Nature. 1982 Aug 12;298(5875):655–657. [PubMed] [Google Scholar]
  • Ymer S, Schofield PR, Draguhn A, Werner P, Köhler M, Seeburg PH. GABAA receptor beta subunit heterogeneity: functional expression of cloned cDNAs. EMBO J. 1989 Jun;8(6):1665–1670. [PMC free article] [PubMed] [Google Scholar]
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