Українська Русский English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2015; 61(5): 107-117

GLYCINE RECEPTOR: MOLECULAR ORGANIZATION AND PATHOLOGY

G.V. Maleeva1,2 , P.D. Bregestovski 1

  1. Brain Dynamic Institute, Aix-Marseille University, Marseille, France;
  2. O.O. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv
DOI: https://doi.org/10.15407/fz61.05.107

Abstract

Glycine receptor is the anion-selective channel, providing fast synaptic transmission in the central nervous system of vertebrates. Together with the nicotinic acetylcholine, GABA and serotonin (5-HT3R) receptors, it belongs to the superfamily of pentameric cys-loop receptors. In this review we briefly describe main functions of these transmembrane proteins, their distribution and molecular architecture. Special attention is paid to recent studies on the molecular physiology of these receptors, as well as on presenting of molecular domains responsible for their dysfunction.

Keywords: cys-loop receptors; anion-selective channels; hyperekplexia; inhibitory synaptic transmission.

Full text: (PDF, in Ukrainian)

References

  1. Bohlhalter S, Mohler H, Fritschy JM. Inhibitory neurotransmission in rat spinal cord: co-localization of glycine- and GABAA-receptors at GABAergic synaptic contacts demonstrated by triple immunofluorescence staining. Brain Res. 1994;642:59–69. CrossRef  
  2. Vesselkin NP, Rio JP, Adanina VO, Repérant J. GABAand glycine-immunoreactive terminals contacting motoneurons in lamprey spinal cord. J Chem Neuroanat. 2000;19:69–80. CrossRef  
  3. Jonas P, Bischofberger J, Sandkühler J. Corelease of two fast neurotransmitters at a central synapse. Science. 1998;281:419–24. CrossRef PubMed
    4.  
  4. Dutertre S, Becker CM, Betz H. Inhibitory glycine receptors: an update. J Biol Chem. 2012;287:40216–23. CrossRef PubMed PubMedCentral
    5.  
  5. Legendre P. The glycinergic inhibitory synapse Cell Mol life Sci. 2001;58:760–93.
    6.  
  6. Lynch JW. Molecular structure and function of the glycine receptor chloride channel. Physiol Rev. 2004;84:1051–95. CrossRef PubMed
    7.  
  7. Miller PS, Smart TG. Binding, activation and modulation of cys-loop receptors. Trends Pharmacol Sci. 2010;31:161–74. CrossRef PubMed
    8.  
  8. Kehoe J, Buldakova S, Acher F, Dent J, Bregestovski P, Bradley J. Aplysia cys-loop glutamate-gated chloride channels reveal convergent evolution of ligand specificity. J Mol Evol. 2009;69:125–41. CrossRef PubMed
    9.  
  9. Tasneem A, Iyer LM, Jakobsson E, Aravind L. Identification of the prokaryotic ligand-gated ion channels and their implications for the mechanisms and origins of animal Cys-loop ion channels. Genome Biol. 2005;6:R4.
    10.  
  10. Karlin A. Emerging structure of the nicotinic acetylcholine receptors. Nat Rev Neurosci. 2002;3:102–14. CrossRef PubMed
    11.  
  11. Unwin N. Structure and action of the nicotinic acetylcholine receptor explored by electron microscopy. FEBS Lett. 2003;555:91–5. CrossRef  
  12. Unwin N. Refined structure of the nicotinic acetylcholine receptor at 4A resolution. J Mol Biol. 2005;346:967–89. CrossRef PubMed
    13.  
  13. Moss SJ, Smart TG. Constructing inhibitory synapses. Nat Rev Neurosci. 2001;2:240-50.
    14.  
  14. Taly A, Corringer PJ, Gruntter T, Prado de Carvalho L, Karplus M, Changeux JP. Implications of the quaternary twist allosteric model for physiology and pathology of nicotinic acetylholine receptors. Prot Natl Acad Sci USA 2006. 103:16965-70.
    15.  
  15. Rajendra S, Schofield R. Molecular mechanisms of inherited startle syndrome. Trends Neurosci. 1995;18:80-2. CrossRef  
  16. Brejc K, Dijk WJ, Klaassen RV, Schuurmans M, Der Oost J, SmitAB, SixmaTK. Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors. Nature. 2001;411:269–76. CrossRef PubMed
    17.  
  17. Dellisanti CD, Yao Y, Stroud JC, Wang ZZ, Chen L. Crystal structure of the extracellular domain of nAChR alpha1 bound to alpha-bungarotoxin at 1.94 A resolution. Nat Neurosci. 2007;10:953–62. CrossRef PubMed
    18.  
  18. Hilf RJ, Dutzler R. X-ray structure of a prokaryotic pentameric ligand-gated ion channel. Nature. 2008;452:375–9. CrossRef PubMed
    19.  
  19. Bocquet N, Nury H, Baaden M, Le Poupon C, Changeux JP, Delarue M, Corringer PJ. X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation. Nature. 2009;457:111–4. CrossRef PubMed
    20.  
  20. Corringer PJ, Poitevin F, Prevost MS, Sauguet L, Delarue M, Changeux JP. Structure and pharmacology of pentameric receptor channels: from bacteria to brain. Structure. 2012;20:941–56. CrossRef PubMed
    21.  
  21. Webb TI, Lynch JW. Molecular pharmacology of the glycine receptor chloride channel. Curr Pharm Des. 2007;13:2350–67. CrossRef  
  22. Corringer PJ, Le Novère N, Changeux JP. Nicotinic receptors at the amino acid level. Annu Rev Pharmacol Toxicol. 2000;40:431–58. CrossRef PubMed
    23.  
  23. Pless SA, Millen KS, Hanek AP, Lynch JW, Lester HA, Lummis SC, Dougherty DA. A cation- π interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue. J Neurosci. 2008;28:10937–42. CrossRef PubMed PubMedCentral
    24.  
  24. Miyazawa A, Fujiyoshi Y, Unwin N. Structure and gating mechanism of the acetylcholine receptor pore. Nature. 2003;423:949–55. CrossRef PubMed
    25.  
  25. Hilf RJ, Dutzler R. Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel. Nature. 2009;457:115–8. CrossRef PubMed
    26.  
  26. Bregestovski P. Architecture of receptor-operated ion channels of biological membranes. Biophysics (Oxf). 2011;56:51–64. CrossRef  
  27. Pfeiffer F, Graham D, Betz H. Purification by affinity chromatography of the glycine receptor of rat spinal cord. J Biol Chem. 1982;257:9389–93.
    28.  
  28. Kirsch J, Langosch D, Prior P, Littauer UZ, Schmitt B, Betz H. The 93-kDa glycine receptor-associated protein binds to tubulin. J Biol Chem. 1991;266:22242–5.
    29.  
  29. Grenningloh G, Rienitz A, Schmitt B, Methfessel C, Zensen M, Beyreuther K, Gundelfinger ED, Betz H. Molecular cloning of the antagonist-binding subunit of the glycine receptor. J Recept Res. 1988;8:183–93. CrossRef PubMed
    30.  
  30. Grenningloh G, Schmieden V, Schofield PR, Seeburg PH, Siddique T, Mohandas TK, Becker C., Betz H. Alpha subunit variants of the human glycine receptor: primary structures, functional expression and chromosomal localization of the corresponding genes. EMBO J. 1990;9:771–6.
    31.  
  31. David-Watine B, Goblet C, De Saint Jan D, Fucile S, Devignot V, Bregestovski P, Korn H. Cloning, expression and electrophysiological characterization of glycine receptor alpha subunit from zebrafish. Neuroscien. 1999;90:303–17. CrossRef  
  32. Devignot V, Prado de Carvalho L, Bregestovski P, Goblet C. A novel glycine receptor αZ1 subunit variant in the zebrafish brain. Neuroscience. 2003;122:449–57. CrossRef  
  33. Imboden M, De Saint Jan D, Leulier F, Korn H, Goblet C, Bregestovski P. Isolation and characterization of an alpha 2-type zebrafish glycine receptor subunit. Neuroscience. 2001;103:799–810. CrossRef  
  34. Imboden M, Devignot V, Goblet C. Phylogenetic relationships and chromosomal location of five distinct glycine receptor subunit genes in the teleost Danio rerio. Dev Genes Evol. 2001;211:415–22. CrossRef PubMed
    35.  
  35. Bormann J, Rundström N, Betz H, Langosch D. Residues within transmembrane segment M2 determine chloride conductance of glycine receptor homo- and heterooligomers. EMBO J. 1994;13:1493.
    36.  
  36. Grenningloh G, Pribilla I, Prior P, Multhaup G, Beyreuther K, Taleb O, Betz H. Cloning and expression of the 58 kd beta subunit of the inhibitory glycine receptor. Neuron. 1990;4:963–70. CrossRef  
  37. Meyer G, Kirsch J, Betz H, Langosch D. Identification of a gephyrin binding motif on the glycine receptor subunit. Neuron. 1995;15:563–72. CrossRef  
  38. Kirsch J, Betz H. The postsynaptic protein gephyrin localization is regulated of the glycine receptor-associated by the cytoskeleton. J Neurosci. 1995;75:4148–56.
    39.  
  39. Kneussel M, Betz H. Receptors, gephyrin and gephyrinassociated proteins: novel insights into the assembly of inhibitory postsynaptic membrane specializations. J Physiol. 2000;525:1–9. CrossRef PubMed PubMedCentral
    40.  
  40. Pribilla I, Takagi T, Langosch D, Bormann J, Betz H, Pribilla I. The atypical M2 segment of the subunit confers picrotoxinin resistance to inhibitory glycine receptor channels. EMBO J. 1992;11:4305–11.
    41.  
  41. Lynch JW, Rajenda S, Barry PH, Schofield P. Mutations affecting the glycine agonist transduction mechanism convert the competitive antagonist, picrotoxin into an allosteric potentiator. J Biol Chem. 1995;270:13799–806. CrossRef PubMed
    42.  
  42. Yang Z, Cromer BA, Harvey RJ, Parker MW, Lynch JW. A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor pore. J Neurochem. 2007;103:580–9. CrossRef PubMed
    43.  
  43. Zhorov BS, Bregestovski PD. Chloride channels of glycine and GABA receptors with blockers: Monte Carlo minimization and structure-activity relationships. Biophys J. 2000;78:1786–803. CrossRef  
  44. Malosio M, Marqueze B, Pouey A, Kuhse J, Betz H. Widespread expression of glycine receptor subunit mRNAs in the adult and developing rat brain. EMBO J. 1991;10:2401–9.
    45.  
  45. Kim EY, Schrader N, Vannier C. Deciphering the structural framework of glycine receptor anchoring by gephyrin. EMBO J. 2006;25:1385–95. CrossRef PubMed PubMedCentral
    46.  
  46. Bedet C, Bruusgaard JC, Groth-Pedersen L, Eimer S, Triller A, Vannier C. Regulation of gephyrin assembly and glycine receptor synaptic stability. J Biol Chem. 2006;281:30046–56. CrossRef PubMed
    47.  
  47. Watanabe E, Akagi H. Distribution patterns of mRNAs encoding glycine receptor channels in the developing rat spinal cord. Neurosci Res. 1995;23:377–82. CrossRef  
  48. Kungel M, Friauf E. Physiology and pharmacology of native glycine receptors in developing rat auditory brainstem neurons. Brain Res Dev. 1997;102:157–65. CrossRef  
  49. Wang F, Xiao C, Ye JH. Taurine activates excitatory nonsynaptic glycine receptors on dopamine neurones in ventral tegmental area of young rats. J Physiol. 2005;2:503–16. CrossRef PubMed PubMedCentral
    50.  
  50. Takahashi T, Momiyama A, Hirai K, Hishinuma F, Akagi H. Functional correlation of fetal and adult forms of glycine receptors with developmental changes in inhibitory synaptic receptor channels. Neuron. 1992;9:1155–61. CrossRef  
  51. Veruki ML, Gill SB, Hartveit E. Spontaneous IPSCs and glycine receptors with slow kinetics in wide-field amacrine cells in the mature rat retina. J Physiol. 2007;581:203–19. CrossRef PubMed PubMedCentral
    52.  
  52. Lynch JW. Native glycine receptor subtypes and their physiological roles. Neuropharmacology. 2009;56:303–9. CrossRef PubMed
    53.  
  53. Haverkamp S, Müller U, Harvey K, Harvey RJ, Betz H, Wässle H. Diversity of glycine receptors in the mouse retina: localization of the alpha3 subunit. J Comp Neurol. 2003;465:524–39. CrossRef PubMed
    54.  
  54. Harvey RJ, Depner UB, Wässle H, Ahmadi S, Heindl C, Reinold H, Smart TG, Harvey K, Schütz B, Abo-Salem OM, Zimmer A, Poisbeau P, Welzl H, Wolfer DP, Betz H, Zeilhofer HU, Müller U. GlyR alpha3: an essential target for spinal PGE2-mediated inflammatory pain sensitization. Science. 2004;304:884–7. CrossRef PubMed
    55.  
  55. Harvey RJ, Schmieden V, Von Holst A, Laube B, Rohrer H, Betz H. Glycine receptors containing the alpha4 subunit in the embryonic sympathetic nervous system, spinal cord and male genital ridge. Eur J Neurosci. 2000;12:994–1001. CrossRef PubMed
    56.  
  56. Heinze L, Harvey RJ, Haverkamp S, Wassle H. Diversity of glycine receptors in the mouse retina: localization of the α4 subunit. J Comp Neurol. 2007;500:693–707. CrossRef PubMed
    57.  
  57. Burzomato V, Beato M, Groot-Kormelink PJ, Colquhoun D, Sivilotti LG. Single-channel behavior of heteromeric alpha1beta glycine receptors: an attempt to detect a conformational change before the channel opens. J Neurosci. 2004;24:10924–40. CrossRef PubMed
    58.  
  58. Grudzinska J, Schemm R, Haeger S, Nicke A, Schmalzing G, Betz H, Laube B. The beta subunit determines the ligand binding properties of synaptic glycine receptors. Neuron. 2005;45:727–39. CrossRef PubMed
    59.  
  59. Yang Z, Taran E, Webb TI, Lynch JW. Stoichiometry and subunit arrangement of α1β glycine receptors as determined by atomic force microscopy. Biochemistry. 2012;51:5229–31. CrossRef PubMed
    60.  
  60. Durisic N, Godin AG, Wever CM, Heyes CD, Lakadamyali M, Dent JA. Stoichiometry of the human glycine receptor revealed by direct subunit counting. J Neurosci. 2012;32:12915–20. CrossRef PubMed PubMedCentral
    61.  
  61. Kneussel M, Betz H. Clustering of inhibitory neurotransmitter receptors at developing postsynaptic sites: the membrane activation model. Trends Neurosci. 2000;23:429–35. CrossRef  
  62. Andermann F, Keene DL, Andermann E, Quesney LF. Startle disease or hyperekplexia: further delineation of the syndrome. Brain. 1980;103:985–97. CrossRef PubMed
    63.  
  63. Lanska DJ. The history of movement disorders. In: Fingers, Boller F, Tyler K, eds. Handbook of clinical neurology. Elsevier B.V. 2010.
    64.  
  64. Bakker MJ, van Dijk JG, van den Maagdenberg AM, Tijssen MA. Startle syndromes. Lancet Neurol. 2006;5:513–24. CrossRef  
  65. Shiang R, Ryan SG, Zhu YZ, Hahn A, O'Connell P, Wasmuth J. Mutations in the alpha 1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia. Nat Genet. 1993;5:351-8. CrossRef PubMed
    66.  
  66. Chung SK, Bode A, Cushion TD, Thomas RH, Hunt C, Wood SE, Pickrell WO, Drew CJ, Yamashita S, Shiang R, Leiz S, Longardt AC, Raile V, Weschke B, Puri RD, Verma IC, Harvey RJ, Ratnasinghe DD, Parker M, Rittey C, Masri A, Lingappa L, Howell OW, Vanbellinghen JF, Mullins JG, Lynch JW, Rees MI. GLRB is the third major gene of effect in hyperekplexia. Hum Mol Genet. 2013;22:927–40. CrossRef PubMed
    67.  
  67. Rees MI, Lewis TM, Kwok JB, Mortier GR, Govaert P, Snell RG, Schofield PR, Owen MJ. Hyperekplexia associated with compound heterozygote mutations in the beta-subunit of the human inhibitory glycine receptor (GLRB). Hum Mol Genet. 2002;11:853–60. CrossRef PubMed
    68.  
  68. Gimenez C, Perez-Siles G, Martinez-Villarreal J, ArribasGonzalez E, Jimenez E, Nunez E, de Juan-Sanz J, Fernandez-Sanchez E, Garcia-Tardon N, Ibanez I, Romanelli V, Nevado J, James VM, Topf M, Chung SK, Thomas RH, Desviat LR, Aragon C, Zafra F, Rees MI, Lapunzina P, Harvey RJ, Lopez- Corcuera B. A novel dominant hyperekplexia mutation Y705C alters trafficking and biochemical properties of the presynaptic glycine transporter GlyT2. J Biol Chem. 2012;287:28986–9002. CrossRef PubMed PubMedCentral
    69.  
  69. Rees MI, Harvey K, Pearce BR, Chung SK, Duguid IC, Thomas P, Beatty S, Graham GE, Armstrong L, Shiang R, Abbott KJ, Zuberi SM, Stephenson JB, Owen MJ, Tijssen MA, van den Maagdenberg AM, Smart TG, Supplisson S, Harvey RJ. Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease. Nat Genet. 2006;38:801–6. CrossRef PubMed PubMedCentral
    70.  
  70. Rees MI, Harvey K, Ward H, White JH, Evans L, Duguid IC, Hsu CC, Coleman SL, Miller J, Baer K, Waldvogel HJ, Gibbon F, Smart TG, Owen MJ, Harvey RJ, Snell RG. Isoform heterogeneity of the human gephyrin gene (GPHN), binding domains to the glycine receptor, and mutation analysis in hyperekplexia. J Biol Chem. 2003;278:24688–96. CrossRef PubMed
    71.  
  71. Harvey K, Duguid IC, Alldred MJ, Beatty SE, Ward H, Keep NH, Lingenfelter SE, Pearce BR, Lundgren J, Owen MJ, Smart TG, Luscher B, Rees MI, Harvey RJ. The GDP-GTP exchange factor collybistin: an essential determinant of neuronal gephyrin clustering. J Neurosci. 2004;24:5816–26. CrossRef PubMed
    72.  
  72. Bode A, Lynch JW. The impact of human hyperekplexia mutations on glycine receptor structure and function. Molecular Brain. 2014;7:2. CrossRef PubMed PubMedCentral
    73.  
  73. Chung SK, Vanbellinghen JF, Mullins JG, Robinson A, Hantke J, Hammond CL, Gilbert DF, Freilinger M, Ryan M, Kruer MC, Masri A, Gurses C, Ferrie C, Harvey K, Shiang R, Christodoulou J, Andermann F, Andermann E, Thomas RH, Harvey RJ, Lynch JW, Rees MI. Pathophysiological mechanisms of dominant and recessive GLRA1 mutations in hyperekplexia. J Neurosci. 2010;30:9612–20. CrossRef PubMed
    74.  
  74. Bode A, Wood SE, Mullins JG, Keramidas A, Cushion TD, Thomas RH, Pickrell WO, Drew CJ, Masri A, Jones EA, Vassallo G, Born AP, Alehan F, Aharoni S, Bannasch G, Bartsch M, Kara B, Krause A, Karam EG, Matta S, Jain V, Mandel H, Freilinger M, Graham GE, Hobson E, Chatfield S, Vincent-Delorme C, Rahme JE, Afawi Z, Berkovic SF, Howell OW, Vanbellinghen JF, Rees MI, Chung SK, Lynch JW. New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms. J Biol Chem. 2013;288:33745–59. CrossRef PubMed PubMedCentral
    75.  
  75. Rees MI, Andrew M, Jawad S, Owen MJ. Evidence for recessive as well as dominant forms of startle disease (hyperekplexia) caused by mutations in the alpha 1 subunit of the inhibitory glycine receptor. Hum Mol Genet. 1994;3:2175–9. CrossRef PubMed
    76.  
  76. Laube B, Maskay G, Schemm R, Betz H. Modulation of glycine receptor function: a novel approach for therapeutic intervention at inhibitory synapse? Trends in Pharmacol Sci. 2002;23:519-27.
    77.  
  77. Bode A, Lynch JW. Analysis of hyperekplexia mutations identifies transmembrane domain rearrangements that mediate glycine receptor activation. J Biol Chem. 2013;288:33760–71. CrossRef PubMed PubMedCentral
    78.  
  78. Elmslie FV, Hutchings SM, Spencer V, Curtis A, Covanis T, Gardiner RM, Rees M. Analysis of GLRA1 in hereditary and sporadic hyperekplexia: a novel mutation in a family cosegregating for hyperekplexia and spastic paraparesis. J Med Genet. 1996;33:435–6. CrossRef PubMed PubMedCentral
    79.  
  79. Shiang R, Ryan SG, Zhu YZ, Fielder TJ, Allen RJ, Fryer A, Yamashita S, O'Connell P, Wasmuth JJ. Mutational analysis of familial and sporadic hyperekplexia. Ann Neurol. 1995;38:85–91. CrossRef PubMed
    80.  
  80. Langosch D, Laube B, Rundstrom N, Schmieden V, Bormann J, Betz H. Decreased agonist affinity and chloride conductance of mutant glycine receptors associated with human hereditary hyperekplexia. EMBO J. 1994;13:4223–8.
    81.  
  81. Maksay G, Biro T, Laube B. Hyperekplexia mutation of glycine receptors: decreased gating efficacy with altered binding thermodynamics. Biochem Pharmacol. 2002;64:285–8. CrossRef  
  82. Rajendra S, Lynch JW, Pierce KD, French CR, Barry PH, Schofield PR. Startle disease mutations reduce the agonist sensitivity of the human inhibitory glycine receptor. J Biol Chem. 1994;269:18739–42.
    83.  
  83. Keramidas A, Moorhouse AJ, Schofield PR, Barry PH. Ligand-gated ion channels: mechanisms underlying ion selectivity. Prog Biophys Mol Biol. 2004;86:161–204. CrossRef PubMed
    84.  
  84. Lape R, Plested AJ, Moroni M, Colquhoun D, Sivilotti LG. The alpha1K276E startle disease mutation reveals multiple intermediate states in the gating of glycine receptors. J Neurosci. 2012;32:1336–52. CrossRef PubMed
    85.  
  85. Lewis TM, Sivilotti LG, Colquhoun D, Gardiner RM, Schoepfer R, Rees M. Properties of human glycine receptors containing the hyperekplexia mutation alpha1(K276E), expressed in Xenopus oocytes. J Physiol. 1998;507(Pt 1):25–40.
    86.  
  86. Milani N, Dalpra L, del Prete A, Zanini R, Larizza L. A novel mutation (Gln266 - > His) in the alpha 1 subunit of the inhibitory glycine-receptor gene (GLRA1) in hereditary hyperekplexia. Am J Hum Genet. 1996;58:420–2.
    87.  
  87. Becker K, Breitinger HG, Humeny A, Meinck HM, Dietz B, Aksu F, Becker CM. The novel hyperekplexia allele GLRA1(S267N) affects the ethanol site of the glycine receptor. Eur J Hum Genet. 2008;16:223–8. CrossRef PubMed
    88.  
  88. del Giudice EM, Coppola G, Bellini G, Cirillo G, Scuccimarra G, Pascotto A. A mutation (V260M) in the middle of the M2 pore-lining domain of the glycine receptor causes hereditary hyperekplexia. Eur J Hum Genet. 2001;9:873–6. CrossRef PubMed
    89.  
  89. Saul B, Kuner T, Sobetzko D, Brune W, Hanefeld F, Meinck HM, Becker CM. Novel GLRA1 missense mutation (P250T) in dominant hyperekplexia defines an intracellular determinant of glycine receptor channel gating. J Neurosci. 1999;19:869–7.
    90.  
  90. Breitinger HG, Lanig H, Vohwinkel C, Grewer C, Breitinger U, Clark T, Becker CM. Molecular dynamics simulation links conformation of a poreflanking region to hyperekplexia-related dysfunction of the inhibitory glycine receptor. Chem Biol. 2004;11:1339–50. CrossRef PubMed
    91.  
  91. Eulenberg V, Armsen W, Betz H, Gomeza J. Glycine transporters: essential regulators of neurotransmission. Trends Biochem Sci. 2005;30:325-33. CrossRef PubMed
    92.  
  92. Carta E, Chung SK, James VM, Robinson A, Gill JL, Remy N, Vanbellinghen JF, Drew CJ, Cagdas S, Cameron D, Cowan FM, Del Toro M, Graham GE, Manzur AY, Masri A, Rivera S, Scalais E, Shiang R, Sinclair K, Stuart CA, Tijssen MA, Wise G, Zuberi SM, Harvey K, Pearce BR, Topf M, Thomas RH, Supplisson S, Rees MI, Harvey RJ. Mutations in the GlyT2 gene (SLC6A5) are a second major cause of startle disease. J Biol Chem. 2012;287:28975–85. CrossRef PubMed PubMedCentral
© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2020.