Inhibitory glycine receptors: An update

Journal of Biological Chemistry

Volumn 287, Issue 48, 2012, Pages 40216-40223

  Dutertre, Sébastien ^a   Becker, Cord Michael ^b   Betz, Heinrich ^c,d  

^a UNIVERSITY OF QUEENSLAND   (Australia)

^b UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^c MAX PLANCK INSTITUTE FOR MEDICAL RESEARCH   (Germany)

^d MAX PLANCK INSTITUTE OF EXPERIMENTAL MEDICINE   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BRAINSTEM; CENTRAL NERVOUS SYSTEMS; CHLORIDE CHANNELS; GLYCINE RECEPTOR; ISOFORMS; LIGAND-BINDING SITES; SENSORY NEURONS; SPINAL CORDS; VISUAL AND AUDITORY SIGNALS;

CHLORINE COMPOUNDS; MAMMALS; NEURONS;

AMINO ACIDS;

ALCOHOL; ANESTHETIC AGENT; CHLORIDE ION; CYSTEINE LOOP LIGAND GATED ION CHANNEL RECEPTOR; ENDOCANNABINOID; GLUTAMATE GATED ION CHANNEL; GLYCINE ALPHA1BETA RECEPTOR; GLYCINE RECEPTOR; GLYCINE RECEPTOR AGONIST; GLYCINE RECEPTOR ALPHA1; GLYCINE RECEPTOR ALPHA2; GLYCINE RECEPTOR ALPHA3; GLYCINE RECEPTOR ALPHA4; GLYCINE RECEPTOR CHLORIDE CHANNEL; GLYCINE TRANSPORTER 2; ION CHANNEL; ISOPROTEIN; IVERMECTIN; NEUROSTEROID; PICROTOXIN; STRYCHNINE; UNCLASSIFIED DRUG; ZINC ION;

ALLOSTERISM; AMINO TERMINAL SEQUENCE; BINDING AFFINITY; CENTRAL NERVOUS SYSTEM; CHLORIDE CONDUCTANCE; CHLORIDE TRANSPORT; CHRONIC PAIN; CRYSTAL STRUCTURE; DRUG BINDING; DRUG BINDING SITE; EXCITATORY POSTSYNAPTIC POTENTIAL; GENE; GLRA1 GENE; GLRA3 GENE; GLYRALPHA GENE; GLYRBETA GENE; HETEROZYGOSITY; HUMAN; HYPEREKPLEXIA; HYPERPOLARIZATION; INHIBITORY POSTSYNAPTIC POTENTIAL; MISSENSE MUTATION; NEUROPATHIC PAIN; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PURIFICATION; PROTEIN STRUCTURE; PROTEIN TARGETING; SENSORY NERVE CELL; SHORT SURVEY; SIGNAL TRANSDUCTION; SPASTICITY; SYNAPTIC INHIBITION; SYNAPTOGENESIS;

ANIMALS; BINDING SITES; HUMANS; RECEPTORS, GLYCINE; STRYCHNINE; SYNAPSES;

MAMMALIA; STRYCHNOS TOXIFERA;

EID: 84870021561     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.R112.408229     Document Type: Short Survey

References (100)

1. Legendre, P. (2001) The glycinergic inhibitory synapse. Cell. Mol. Life Sci. 58, 760-793
2. Young, A. B., and Snyder, S. H. (1973) Strychnine binding associated with glycine receptors of the central nervous system. Proc. Natl. Acad. Sci. U.S.A. 70, 2832-2836
3. Pfeiffer, F., Graham, D., and Betz, H. (1982) Purification by affinity chromatography of the glycine receptor of rat spinal cord. J. Biol. Chem. 257, 9389-9393 (Pubitemid 13199102)
4. Betz, H., and Laube, B. (2006) Glycine receptors: recent insights into their structural organization and functional diversity. J. Neurochem. 97, 1600-1610 (Pubitemid 43873655)
5. Lynch, J. W. (2004) Molecular structure and function of the glycine receptor chloride channel. Physiol. Rev. 84, 1051-1095
6. Prior, P., Schmitt, B., Grenningloh, G., Pribilla, I., Multhaup, G., Beyreuther, K., Maulet, Y., Werner, P., Langosch, D., and Kirsch, J. (1992) Primary structure and alternative splice variants of gephyrin, a putative glycine receptor-tubulin linker protein. Neuron 8, 1161-1170
7. Langosch, D., Thomas, L., and Betz, H. (1988) Conserved quaternary structure of ligand-gated ion channels: the postsynaptic glycine receptor is a pentamer. Proc. Natl. Acad. Sci. U.S.A. 85, 7394-7398
8. Burzomato, V., Groot-Kormelink, P. J., Sivilotti, L. G., and Beato, M. (2003) Stoichiometry of recombinant heteromeric glycine receptors revealed by a pore-lining region point mutation. Receptors Channels 9, 353-361 (Pubitemid 38008222)
9. Grudzinska, J., Schemm, R., Haeger, S., Nicke, A., Schmalzing, G., Betz, H., and Laube, B. (2005) The β subunit determines the ligand binding properties of synaptic glycine receptors. Neuron 45, 727-739 (Pubitemid 40320707)
10. Yang, Z., Taran, E., Webb, T. I., and Lynch, J. W. (2012) Stoichiometry and subunit arrangement of α1β glycine receptors as determined by atomic force microscopy. Biochemistry 51, 5229-5231
11. Grenningloh, G., Pribilla, I., Prior, P., Multhaup, G., Beyreuther, K., Taleb, O., and Betz, H. (1990) Cloning and expression of the 58-kDa β subunit of the inhibitory glycine receptor. Neuron 4, 963-970 (Pubitemid 20208522)
12. Grenningloh, G., Rienitz, A., Schmitt, B., Methfessel, C., Zensen, M., Beyreuther, K., Gundelfinger, E. D., and Betz, H. (1987) The strychnine-binding subunit of the glycine receptor shows homology with nicotinic acetylcholine receptors. Nature 328, 215-220 (Pubitemid 17108270)
13. Grenningloh, G., Schmieden, V., Schofield, P. R., Seeburg, P. H., Siddique, T., Mohandas, T. K., Becker, C. M., and Betz, H. (1990) α subunit variants of the human glycine receptor: primary structures, functional expression and chromosomal localization of the corresponding genes. EMBO J. 9, 771-776
14. Kuhse, J., Schmieden, V., and Betz, H. (1990) Identification and functional expression of a novel ligand binding subunit of the inhibitory glycine receptor. J. Biol. Chem. 265, 22317-22320 (Pubitemid 120014303)
15. Matzenbach, B., Maulet, Y., Sefton, L., Courtier, B., Avner, P., Guénet, J. L., and Betz, H. (1994) Structural analysis of mouse glycine receptor α subunit genes. Identification and chromosomal localization of a novel variant. J. Biol. Chem. 269, 2607-2612 (Pubitemid 24235756)
16. Graham, D., Pfeiffer, F., and Betz, H. (1983) Photoaffinity labelling of the glycine receptor of rat spinal cord. Eur. J. Biochem. 131, 519-525 (Pubitemid 13090874)
17. Griffon, N., Büttner, C., Nicke, A., Kuhse, J., Schmalzing, G., and Betz, H. (1999) Molecular determinants of glycine receptor subunit assembly. EMBO J. 18, 4711-4721 (Pubitemid 29415525)
18. Kneussel, M., and Betz, H. (2000) Clustering of inhibitory neurotransmitter receptors at developing postsynaptic sites: the membrane activation model. Trends Neurosci. 23, 429-435
19. Maas, C., Tagnaouti, N., Loebrich, S., Behrend, B., Lappe-Siefke, C., and Kneussel, M. (2006) Neuronal cotransport of glycine receptor and the scaffold protein gephyrin. J. Cell Biol. 172, 441-451 (Pubitemid 43187940)
20. Meyer, G., Kirsch, J., Betz, H., and Langosch, D. (1995) Identification of a gephyrin binding motif on the glycine receptor β subunit. Neuron 15, 563-572
21. del Pino, I., Paarmann, I., Karas, M., Kilimann, M. W., and Betz, H. (2011) The trafficking proteins vacuolar protein sorting 35 and neurobeachin interact with the glycine receptor β subunit. Biochem. Biophys. Res. Commun. 412, 435-440
22. Corringer, P. J., Le Novère, N., and Changeux, J. P. (2000) Nicotinic receptors at the amino acid level. Annu. Rev. Pharmacol. Toxicol. 40, 431-458
23. Oertel, J., Villmann, C., Kettenmann, H., Kirchhoff, F., and Becker, C. M. (2007) A novel glycine receptor β subunit splice variant predicts an unorthodox transmembrane topology. Assembly into heteromeric receptor complexes. J. Biol. Chem. 282, 2798-2807 (Pubitemid 47084343)
24. Miller, P. S., Harvey, R. J., and Smart, T. G. (2004) Differential agonist sensitivity of glycine receptor α2 subunit splice variants. Br. J. Pharmacol. 143, 19-26 (Pubitemid 39280020)
25. Nikolic, Z., Laube, B., Weber, R. G., Lichter, P., Kioschis, P., Poustka, A., Mülhardt, C., and Becker, C. M. (1998) The human glycine receptor subunit α3. GLRa3 gene structure, chromosomal localization, and functional characterization of alternative transcripts. J. Biol. Chem. 273, 19708-19714 (Pubitemid 28367029)
26. Melzer, N., Villmann, C., Becker, K., Harvey, K., Harvey, R. J., Vogel, N., Kluck, C. J., Kneussel, M., and Becker, C. M. (2010) Multifunctional basic motif in the glycine receptor intracellular domain induces subunit-specific sorting. J. Biol. Chem. 285, 3730-3739
27. Meier, J. C., Henneberger, C., Melnick, I., Racca, C., Harvey, R. J., Heinemann, U., Schmieden, V., and Grantyn, R. (2005) RNA editing produces glycine receptor α3(P185L), resulting in high agonist potency. Nat. Neurosci. 8, 736-744 (Pubitemid 43085839)
28. Breitinger, U., Breitinger, H. G., Bauer, F., Fahmy, K., Glockenhammer, D., and Becker, C. M. (2004) Conserved high affinity ligand binding and membrane association in the native and refolded extracellular domain of the human glycine receptor α1 subunit. J. Biol. Chem. 279, 1627-1636 (Pubitemid 38084428)
29. Miyazawa, A., Fujiyoshi, Y., and Unwin, N. (2003) Structure and gating mechanism of the acetylcholine receptor pore. Nature 423, 949-955 (Pubitemid 36806903)
30. Brejc, K., van Dijk, W. J., Klaassen, R. V., Schuurmans, M., van Der Oost, J., Smit, A. B., and Sixma, T. K. (2001) Crystal structure of an AChbinding protein reveals the ligand-binding domain of nicotinic receptors. Nature 411, 269-276 (Pubitemid 32467026)
31. Laube, B., Maksay, G., Schemm, R., and Betz, H. (2002) Modulation of glycine receptor function: a novel approach for therapeutic intervention at inhibitory synapses? Trends Pharmacol. Sci. 23, 519-527 (Pubitemid 35292372)
32. Nevin, S. T., Cromer, B. A., Haddrill, J. L., Morton, C. J., Parker, M. W., and Lynch, J. W. (2003) Insights into the structural basis for zinc inhibition of the glycine receptor. J. Biol. Chem. 278, 28985-28992 (Pubitemid 36935810)
33. Hibbs, R. E., and Gouaux, E. (2011) Principles of activation and permeation in an anion-selective Cys loop receptor. Nature 474, 54-60
34. Rajendra, S., Lynch, J. W., Pierce, K. D., French, C. R., Barry, P. H., and Schofield, P. R. (1995) Mutation of an arginine residue in the human glycine receptor transforms β-alanine and taurine from agonists into competitive antagonists. Neuron 14, 169-175
35. Dutertre, S., Drwal, M., Laube, B., and Betz, H. (2012) Probing the pharmacological properties of distinct subunit interfaces within heteromeric glycine receptors reveals a functional ββ agonist-binding site. J. Neurochem. 122, 38-47
36. Miller, P. S., Topf, M., and Smart, T. G. (2008) Mapping a molecular link between allosteric inhibition and activation of the glycine receptor. Nat. Struct. Mol. Biol. 15, 1084-1093
37. Blednov, Y. A., Benavidez, J. M., Homanics, G. E., and Harris, R. A. (2012) Behavioral characterization of knock-in mice with mutations M287L and Q266I in the glycine receptor α1 subunit. J. Pharmacol. Exp. Ther. 340, 317-329
38. 2+ as an essential endogenous modulator of glycinergic neurotransmission. Neuron 52, 679-690
39. Maksay, G., Laube, B., Schemm, R., Grudzinska, J., Drwal, M., and Betz, H. (2009) Different binding modes of tropeines mediating inhibition and potentiation of α1 glycine receptors. J. Neurochem. 109, 1725-1732
40. Miller, P. S., Da Silva, H. M., and Smart, T. G. (2005) Molecular basis for zinc potentiation at strychnine-sensitive glycine receptors. J. Biol. Chem. 280, 37877-37884 (Pubitemid 41642399)
41. Xiong, W., Wu, X., Lovinger, D. M., and Zhang, L. (2012) A common molecular basis for exogenous and endogenous cannabinoid potentiation of glycine receptors. J. Neurosci. 32, 5200-5208
42. Mihic, S. J., Ye, Q., Wick, M. J., Koltchine, V. V., Krasowski, M. D., Finn, S. E., Mascia, M. P., Valenzuela, C. F., Hanson, K. K., Greenblatt, E. P., Harris, R. A., and Harrison, N. L. (1997) Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors. Nature 389, 385-389 (Pubitemid 27415220)
43. Perkins, D. I., Trudell, J. R., Crawford, D. K., Alkana, R. L., and Davies, D. L. (2010) Molecular targets and mechanisms for ethanol action in glycine receptors. Pharmacol. Ther. 127, 53-65
44. Yévenes, G. E., and Zeilhofer, H. U. (2011) Molecular sites for the positive allosteric modulation of glycine receptors by endocannabinoids. PLoS ONE 6, e23886
45. Liu, J., Wu, D. C., and Wang, Y. T. (2010) Allosteric potentiation of glycine receptor chloride currents by glutamate. Nat. Neurosci. 13, 1225-1232
46. Haeger, S., Kuzmin, D., Detro-Dassen, S., Lang, N., Kilb, M., Tsetlin, V., Betz, H., Laube, B., and Schmalzing, G. (2010) An intramembrane aromatic network determines pentameric assembly of Cys loop receptors. Nat. Struct. Mol. Biol. 17, 90-98
47. Lynch, J. W., Han, N. L., Haddrill, J., Pierce, K. D., and Schofield, P. R. (2001) The surface accessibility of the glycine receptor M2-M3 loop is increased in the channel open state. J. Neurosci. 21, 2589-2599 (Pubitemid 32298201)
48. Xu, M., and Akabas, M. H. (1996) Identification of channel-lining residues in the M2 membrane-spanning segment of the GABAA receptor α1 subunit. J. Gen. Physiol. 107, 195-205 (Pubitemid 26076087)
49. Bocquet, N., Nury, H., Baaden, M., Le Poupon, C., Changeux, J. P., Delarue, M., and Corringer, P. J. (2009) X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation. Nature 457, 111-114
50. Lewis, T. M., Sivilotti, L. G., Colquhoun, D., Gardiner, R. M., Schoepfer, R., and Rees, M. (1998) Properties of human glycine receptors containing the hyperekplexia mutation α1(K276E), expressed in Xenopus oocytes. J. Physiol. 507, 25-40 (Pubitemid 28102673)
51. Pless, S. A., Leung, A. W., Galpin, J. D., and Ahern, C. A. (2011) Contributions of conserved residues at the gating interface of glycine receptors. J. Biol. Chem. 286, 35129-35136
52. Keramidas, A., Moorhouse, A. J., Pierce, K. D., Schofield, P. R., and Barry, P. H. (2002) Cation-selective mutations in the M2 domain of the inhibitory glycine receptor channel reveal determinants of ion-charge selectivity. J. Gen. Physiol. 119, 393-410 (Pubitemid 34522287)
53. Bormann, J., Hamill, O. P., and Sakmann, B. (1987) Mechanism of anion permeation through channels gated by glycine and γ-aminobutyric acid in mouse cultured spinal neurons. J. Physiol. 385, 243-286 (Pubitemid 17048935)
54. Langosch, D., Laube, B., Rundström, N., Schmieden, V., Bormann, J., and Betz, H. (1994) Decreased agonist affinity and chloride conductance of mutant glycine receptors associated with human hereditary hyperekplexia. EMBO J. 13, 4223-4228 (Pubitemid 24295194)
55. 3A receptor from cationic to anionic reveals a conserved feature of the ligand-gated ion channel superfamily. J. Biol. Chem. 276, 10977-10983
56. Lee, D. J., Keramidas, A., Moorhouse, A. J., Schofield, P. R., and Barry, P. H. (2003) The contribution of proline 250 (P-2′) to pore diameter and ion selectivity in the human glycine receptor channel. Neurosci. Lett. 351, 196-200 (Pubitemid 37410337)
57. Pribilla, I., Takagi, T., Langosch, D., Bormann, J., and Betz, H. (1992) The atypical M2 segment of the βsubunit confers picrotoxinin resistance to inhibitory glycine receptor channels. EMBO J. 11, 4305-4311
58. Dibas, M. I., Gonzales, E. B., Das, P., Bell-Horner, C. L., and Dillon, G. H. (2002) Identification of a novel residue within the second transmembrane domain that confers use-facilitated block by picrotoxin in glycine α1 receptors. J. Biol. Chem. 277, 9112-9117 (Pubitemid 34952987)
59. Lynch, J. W., Rajendra, S., Barry, P. H., and Schofield, P. R. (1995) Mutations affecting the glycine receptor agonist transduction mechanism convert the competitive antagonist picrotoxin into an allosteric potentiator. J. Biol. Chem. 270, 13799-13806
60. Yang, Z., Cromer, B. A., Harvey, R. J., Parker, M. W., and Lynch, J. W. (2007) A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor pore. J. Neurochem. 103, 580-589 (Pubitemid 47498044)
61. Lu, H., and Xu, T. L. (2002) The general anesthetic pentobarbital slows desensitization and deactivation of the glycine receptor in the rat spinal dorsal horn neurons. J. Biol. Chem. 277, 41369-41378 (Pubitemid 35257437)
62. A receptor. J. Neurosci. 21, RC136
63. Nury, H., Van Renterghem, C., Weng, Y., Tran, A., Baaden, M., Dufresne, V., Changeux, J. P., Sonner, J. M., Delarue, M., and Corringer, P. J. (2011) X-ray structures of general anaesthetics bound to a pentameric ligandgated ion channel. Nature 469, 428-431
64. A receptor anesthetic binding site at subunit interfaces by photolabeling with an etomidate analog. J. Neurosci. 26, 11599-11605
65. Lynagh, T., Webb, T. I., Dixon, C. L., Cromer, B. A., and Lynch, J. W. (2011) Molecular determinants of ivermectin sensitivity at the glycine receptor chloride channel. J. Biol. Chem. 286, 43913-43924
66. Ryan, S. G., Buckwalter, M. S., Lynch, J. W., Handford, C. A., Segura, L., Shiang, R., Wasmuth, J. J., Camper, S. A., Schofield, P., and O'Connell, P. (1994) A missense mutation in the gene encoding the α1 subunit of the inhibitory glycine receptor in the spasmodic mouse. Nat. Genet. 7, 131-135 (Pubitemid 24174649)
67. Saul, B., Schmieden, V., Kling, C., Mülhardt, C., Gass, P., Kuhse, J., and Becker, C. M. (1994) Point mutation of glycine receptor α1 subunit in the spasmodic mouse affects agonist responses. FEBS Lett. 350, 71-76
68. Buckwalter, M. S., Cook, S. A., Davisson, M. T., White, W. F., and Camper, S. A. (1994) A frameshift mutation in the mouse α1 glycine receptor gene (Glra1) results in progressive neurological symptoms and juvenile death. Hum. Mol. Genet. 3, 2025-2030
69. spd-ot, a glycine receptor subunit mutant, by independently expressed C-terminal domains. J. Neurosci. 29, 2440-2452
70. Singer, J. H., Talley, E. M., Bayliss, D. A., and Berger, A. J. (1998) Development of glycinergic synaptic transmission to rat brainstem motoneurons. J. Neurophysiol. 80, 2608-2620 (Pubitemid 28546189)
71. Wässle, H., Heinze, L., Ivanova, E., Majumdar, S., Weiss, J., Harvey, R. J., and Haverkamp, S. (2009) Glycinergic transmission in the mammalian retina. Front. Mol. Neurosci. 2, 6
72. Weltzien, F., Puller, C., O'Sullivan, G. A., Paarmann, I., and Betz, H. (2012) Distribution of the glycine receptor β subunit in the mouse CNS as revealed by a novel monoclonal antibody. J. Comp. Neurol. 520, 3962-3981
73. Hoch, W., Betz, H., and Becker, C. M. (1989) Primary cultures of mouse spinal cord express the neonatal isoform of the inhibitory glycine receptor. Neuron 3, 339-348
74. Weiss, J., O'Sullivan, G. A., Heinze, L., Chen, H. X., Betz, H., and Wässle, H. (2008) Glycinergic input of small-field amacrine cells in the retinas of wild-type and glycine receptor-deficient mice. Mol. Cell. Neurosci. 37, 40-55 (Pubitemid 350299991)
75. Young-Pearse, T. L., Ivic, L., Kriegstein, A. R., and Cepko, C. L. (2006) Characterization of mice with targeted deletion of glycine receptor α2. Mol. Cell. Biol. 26, 5728-5734 (Pubitemid 44134329)
76. Nobles, R. D., Zhang, C., Müller, U., Betz, H., and McCall, M. A. (2012) Selective glycine receptor α2 subunit control of crossover inhibition between the on and off retinal pathways. J. Neurosci. 32, 3321-3332
77. Kallenborn-Gerhardt, W., Lu, R., Lorenz, J., Gao, W., Weiland, J., Del Turco, D., Deller, T., Laube, B., Betz, H., Geisslinger, G., and Schmidtko, A. (2012) Prolonged zymosan-induced inflammatory pain hypersensitivity in mice lacking glycine receptor α2. Behav. Brain Res. 226, 106-111
78. Malosio, M. L., Marquèze-Pouey, B., Kuhse, J., and Betz, H. (1991) Widespread expression of glycine receptor subunit mRNAs in the adult and developing rat brain. EMBO J. 10, 2401-2409 (Pubitemid 21905713)
79. Harvey, R. J., Depner, U. B., Wässle, H., Ahmadi, S., Heindl, C., Reinold, H., Smart, T. G., Harvey, K., Schütz, B., Abo-Salem, O. M., Zimmer, A., Poisbeau, P., Welzl, H., Wolfer, D. P., Betz, H., Zeilhofer, H. U., and Müller, U. (2004) GlyR α3: an essential target for spinal PGE2-mediated inflammatory pain sensitization. Science 304, 884-887 (Pubitemid 38620190)
80. Xiong, W., Cui, T., Cheng, K., Yang, F., Chen, S. R., Willenbring, D., Guan, Y., Pan, H. L., Ren, K., Xu, Y., and Zhang, L. (2012) Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors. J. Exp. Med. 209, 1121-1134
81. Dlugaiczyk, J., Singer, W., Schick, B., Iro, H., Becker, K., Becker, C. M., Zimmermann, U., Rohbock, K., and Knipper, M. (2008) Expression of glycine receptors and gephyrin in the rat cochlea. Histochem. Cell Biol. 129, 513-523
82. Harvey, R. J., Schmieden, V., Von Holst, A., Laube, B., Rohrer, H., and Betz, H. (2000) Glycine receptors containing the α4 subunit in the embryonic sympathetic nervous system, spinal cord and male genital ridge. Eur. J. Neurosci. 12, 994-1001 (Pubitemid 30168778)
83. White, W. F., and Heller, A. H. (1982) Glycine receptor alteration in the mutant mouse spastic. Nature 298, 655-657 (Pubitemid 12099720)
84. Kingsmore, S. F., Giros, B., Suh, D., Bieniarz, M., Caron, M. G., and Seldin, M. F. (1994) Glycine receptor β subunit gene mutation in spastic mouse associated with LINE-1 element insertion. Nat. Genet. 7, 136-141
85. Mülhardt, C., Fischer, M., Gass, P., Simon-Chazottes, D., Guénet, J. L., Kuhse, J., Betz, H., and Becker, C. M. (1994) The spastic mouse: aberrant splicing of glycine receptor βsubunit mRNA caused by intronic insertion of L1 element. Neuron 13, 1003-1015 (Pubitemid 24347312)
86. bspa allele is a splicing signal polymorphism amplified by long interspersed nuclear element insertion. J. Biol. Chem. 287, 31185-31194
87. Reichling, D. B., Kyrozis, A., Wang, J., and MacDermott, A. B. (1994) Mechanisms of GABA and glycine depolarization-induced calcium transients in rat dorsal horn neurons. J. Physiol. 476, 411-421 (Pubitemid 24154202)
88. Kirsch, J., and Betz, H. (1998) Glycine receptor activation is required for receptor clustering in spinal neurons. Nature 392, 717-720 (Pubitemid 28207792)
89. Turecek, R., and Trussell, L. O. (2002) Reciprocal developmental regulation of presynaptic ionotropic receptors. Proc. Natl. Acad. Sci. U.S.A. 99, 13884-13889 (Pubitemid 35215475)
90. Kubota, H., Alle, H., Betz, H., and Geiger, J. R. (2010) Presynaptic glycine receptors on hippocampal mossy fibers. Biochem. Biophys. Res. Commun. 393, 587-591
91. Rivera, C., Voipio, J., Payne, J. A., Ruusuvuori, E., Lahtinen, H., Lamsa, K., Pirvola, U., Saarma, M., and Kaila, K. (1999) The K+/Cl- cotransporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 397, 251-255
92. Becker, C. M., Hoch, W., and Betz, H. (1988) Glycine receptor heterogeneity in rat spinal cord during postnatal development. EMBO J. 7, 3717-3726
93. Takahashi, T., Momiyama, A., Hirai, K., Hishinuma, F., and Akagi, H. (1992) Functional correlation of fetal and adult forms of glycine receptors with developmental changes in inhibitory synaptic receptor channels. Neuron 9, 1155-1161 (Pubitemid 23007185)
94. Bormann, J., Rundström, N., Betz, H., and Langosch, D. (1993) Residues within transmembrane segment M2 determine chloride conductance of glycine receptor homo- and hetero-oligomers. EMBO J. 12, 3729-3737 (Pubitemid 23282748)
95. Shiang, R., Ryan, S. G., Zhu, Y. Z., Hahn, A. F., O'Connell, P., and Wasmuth, J. J. (1993) Mutations in the α1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder hyperekplexia. Nat. Genet. 5, 351-358 (Pubitemid 2000272)
96. Rajendra, S., Lynch, J. W., Pierce, K. D., French, C. R., Barry, P. H., and Schofield, P. R. (1994) Startle disease mutations reduce the agonist sensitivity of the human inhibitory glycine receptor. J. Biol. Chem. 269, 18739-18742 (Pubitemid 24226181)
97. Davies, J. S., Chung, S. K., Thomas, R. H., Robinson, A., Hammond, C. L., Mullins, J. G., Carta, E., Pearce, B. R., Harvey, K., Harvey, R. J., and Rees, M. I. (2010) The glycinergic system in human startle disease: a genetic screening approach. Front. Mol. Neurosci. 3, 8
98. Chung, S. K., Vanbellinghen, J. F., Mullins, J. G., Robinson, A., Hantke, J., Hammond, C. L., Gilbert, D. F., Freilinger, M., Ryan, M., Kruer, M. C., Masri, A., Gurses, C., Ferrie, C., Harvey, K., Shiang, R., Christodoulou, J., Andermann, F., Andermann, E., Thomas, R. H., Harvey, R. J., Lynch, J. W., and Rees, M. I. (2010) Pathophysiological mechanisms of dominant and recessive GLRA1 mutations in hyperekplexia. J. Neurosci. 30, 9612-9620
99. Al-Owain, M., Colak, D., Al-Bakheet, A., Al-Hashmi, N., Shuaib, T., Al-Hemidan, A., Aldhalaan, H., Rahbeeni, Z., Al-Sayed, M., Al-Younes, B., Ozand, P. T., and Kaya, N. (2012) Novel mutation in GLRB in a large family with hereditary hyperekplexia. Clin. Genet. 81, 479-484
100. Hutchinson, M., Waters, P., McHugh, J., Gorman, G., O'Riordan, S., Connolly, S., Hager, H., Yu, P., Becker, C. M., and Vincent, A. (2008) Progressive encephalomyelitis, rigidity, and myoclonus: a novel glycine receptor antibody. Neurology 71, 1291-1292