Genomes and Genes
Gene Symbol: Glra1
Description: glycine receptor, alpha 1
Alias: GLYRA1, glycine receptor subunit alpha-1, glycine receptor 48 kDa subunit, glycine receptor strychnine-binding subunit, glycine receptor, alpha 1 subunit
- Simon E. Phenotypic heterogeneity and disease course in three murine strains with mutations in genes encoding for alpha 1 and beta glycine receptor subunits. Mov Disord. 1997;12:221-8 pubmed..These mutants represent good animal models for elucidation of molecular and cellular issues regarding the glycine receptor and for the study of pathogenetic mechanisms of movement disorders. ..
- Feng G, Tintrup H, Kirsch J, Nichol M, Kuhse J, Betz H, et al. Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity. Science. 1998;282:1321-4 pubmed..The mutant phenotype resembled that of humans with hereditary molybdenum cofactor deficiency and hyperekplexia (a failure of inhibitory neurotransmission), suggesting that gephyrin function may be impaired in both diseases. ..
- Sato Y, Son J, Tucker R, Meizel S. The zona pellucida-initiated acrosome reaction: defect due to mutations in the sperm glycine receptor/Cl(-) channel. Dev Biol. 2000;227:211-8 pubmed..Moreover, a monoclonal antibody against GlyR completely blocked ZP initiation of AR in normal mouse sperm. Our results are consistent with an essential role for the sperm GlyR in the ZP-initiated AR. ..
- Traka M, Seburn K, Popko B. Nmf11 is a novel ENU-induced mutation in the mouse glycine receptor alpha 1 subunit. Mamm Genome. 2006;17:950-5 pubmed..In this article we show that the mutation is in the gene that encodes the glycine receptor alpha 1 subunit (Glra1)...
- Bray C, Son J, Kumar P, Harris J, Meizel S. A role for the human sperm glycine receptor/Cl(-) channel in the acrosome reaction initiated by recombinant ZP3. Biol Reprod. 2002;66:91-7 pubmed
- Koch M, Kling C, Becker C. Increased startle responses in mice carrying mutations of glycine receptor subunit genes. Neuroreport. 1996;7:806-8 pubmedAn exaggerated startle response caused by mutations of the alpha 1 subunit gene of the inhibitory glycine receptor (GLRA1) is the key symptom of human hyperekplexia or startle disease...
- Ruiz Gomez A, Morato E, Garcia Calvo M, Valdivieso F, Mayor F. Localization of the strychnine binding site on the 48-kilodalton subunit of the glycine receptor. Biochemistry. 1990;29:7033-40 pubmed..N-Chlorosuccinimide treatment of [3H]strychnine-labeled 48K polypeptide yielded a single labeled peptide of Mr approximately 7300, and cyanogen bromide gave a labeled peptide of Mr 6200.(ABSTRACT TRUNCATED AT 250 WORDS)..
- Oertel J, Villmann C, Kettenmann H, Kirchhoff F, Becker C. A novel glycine receptor beta subunit splice variant predicts an unorthodox transmembrane topology. Assembly into heteromeric receptor complexes. J Biol Chem. 2007;282:2798-807 pubmed..Rather, the high level of expression in non-neuronal cells having intimate contact with synaptic regions may account for a yet unknown function of this splice variant betaDelta7 in glycinergic neurotransmission. ..
- Büsselberg D, Bischoff A, Becker K, Becker C, Richter D. The respiratory rhythm in mutant oscillator mice. Neurosci Lett. 2001;316:99-102 pubmed..Postsynaptic activity and membrane potential trajectories of respiratory neurones revealed a persistence of GABAergic inhibition and changes in respiratory rhythm and pattern generation. ..
- Burgos C, Castro P, Mariqueo T, Bunster M, GuzmÃ¡n L, Aguayo L. Evidence for Î±-helices in the large intracellular domain mediating modulation of the Î±1-glycine receptor by ethanol and GÎ²Î³. J Pharmacol Exp Ther. 2015;352:148-55 pubmed publisher..Recovery of the sensitivity to ethanol was associated with the existence of a helical conformation similar to Î±1-GlyR, thus being an essential secondary structural requirement for GlyR modulation by ethanol and G protein. ..
- Inoue K, Ueno S, Yamada J, Fukuda A. Characterization of newly cloned variant of rat glycine receptor alpha1 subunit. Biochem Biophys Res Commun. 2005;327:300-5 pubmed..When present with other isoforms, GlyRalpha1del might alter the response to glycine or to other agonists, as this variant expands the potential heterogeneity among glycine receptors. ..
- Miller P, Da Silva H, Smart T. Molecular basis for zinc potentiation at strychnine-sensitive glycine receptors. J Biol Chem. 2005;280:37877-84 pubmed
- Zhou N, Wang C, Zhang S, Wu D. The GLRA1 missense mutation W170S associates lack of Zn2+ potentiation with human hyperekplexia. J Neurosci. 2013;33:17675-81 pubmed publisher..Together, our results reveal a new zinc potentiation site on ?1 GlyRs and a strong link between Zn(2+) modulation and human disease. ..
- Buckwalter M, Testa C, Noebels J, Camper S. Genetic mapping and evaluation of candidate genes for spasmodic, a neurological mouse mutation with abnormal startle response. Genomics. 1993;17:279-86 pubmed..Synteny homology and phenotypic similarities suggest that spasmodic mice may be a genetic model for the inherited human startle disease, hyperekplexia (STHE). ..
- Grenningloh G, Schmieden V, Schofield P, Seeburg P, Siddique T, Mohandas T, et al. 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 pubmed..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. ..
- Becker C, Schmieden V, Tarroni P, Strasser U, Betz H. Isoform-selective deficit of glycine receptors in the mouse mutant spastic. Neuron. 1992;8:283-9 pubmed..Thus, the age-dependent manifestation of spastic symptoms after birth reflects a selective effect of the mutation on the developmental expression of the adult glycine receptor isoform. ..
- Burzomato V, Beato M, Groot Kormelink P, Colquhoun D, Sivilotti L. 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 pubmed..Distinguishing between the two mechanisms will be important for our understanding of the structural dynamics of activation in the nicotinic superfamily and is important for our understanding of mutations in these receptors. ..
- Zhou W, Zhou L, Shi H, Leng Y, Liu B, Zhang S, et al. Expression of glycine receptors and gephyrin in rat medial vestibular nuclei and flocculi following unilateral labyrinthectomy. Int J Mol Med. 2016;38:1481-1489 pubmed publisher..The findings of our study thus suggest that GlyR plays a major role in the recovery of the resting discharge of the deafferented MVN neurons in the central vestibular system. ..
- Handford C, Lynch J, Baker E, Webb G, Ford J, Sutherland G, et al. The human glycine receptor beta subunit: primary structure, functional characterisation and chromosomal localisation of the human and murine genes. Brain Res Mol Brain Res. 1996;35:211-9 pubmed..It also raises the possibility that mutations in the human beta subunit gene may cause inherited disorders of the startle response. ..
- Buckwalter M, Cook S, Davisson M, White W, Camper S. A frameshift mutation in the mouse alpha 1 glycine receptor gene (Glra1) results in progressive neurological symptoms and juvenile death. Hum Mol Genet. 1994;3:2025-30 pubmed..Oscillator is caused by a microdeletion in the gene coding for the alpha 1 subunit of the adult glycine receptor (Glra1)...
- Beato M, Groot Kormelink P, Colquhoun D, Sivilotti L. The activation mechanism of alpha1 homomeric glycine receptors. J Neurosci. 2004;24:895-906 pubmed..Successive binding steps are not identical, implying that binding sites can interact while the channel is shut. These interactions can be interpreted in the light of the topology of the binding sites within a homopentamer. ..
- Shiang R, Ryan S, Zhu Y, 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 pubmed..describe the identification of point mutations in the gene encoding the alpha 1 subunit of the glycine receptor (GLRA1) in STHE patients from four different families...
- Humeny A, Bonk T, Becker K, Jafari Boroujerdi M, Stephani U, Reuter K, et al. A novel recessive hyperekplexia allele GLRA1 (S231R): genotyping by MALDI-TOF mass spectrometry and functional characterisation as a determinant of cellular glycine receptor trafficking. Eur J Hum Genet. 2002;10:188-96 pubmed..Several autosomal dominant and recessive forms of the disorder have been associated with point mutations in GLRA1, the human gene encoding the alpha 1 subunit of the inhibitory glycine receptor...
- Graham B, Schofield P, Sah P, Margrie T, Callister R. Distinct physiological mechanisms underlie altered glycinergic synaptic transmission in the murine mutants spastic, spasmodic, and oscillator. J Neurosci. 2006;26:4880-90 pubmed..Together, these findings show the three mutations disrupt GlyR-mediated inhibition via different physiological mechanisms, and the spastic mutation results in "compensatory" alpha1 homomeric GlyRs at extrasynaptic loci. ..
- Zhao M, Hülsmann S, Winter S, Dutschmann M, Richter D. Calcium-regulated potassium currents secure respiratory rhythm generation after loss of glycinergic inhibition. Eur J Neurosci. 2006;24:145-54 pubmedMutant oscillator mice (Glra1(spd -/-)) are characterized by a developmental loss of glycinergic inhibition...
- Zhang Y, Bode A, Nguyen B, Keramidas A, Lynch J. Investigating the Mechanism by Which Gain-of-function Mutations to the ?1 Glycine Receptor Cause Hyperekplexia. J Biol Chem. 2016;291:15332-41 pubmed publisher..Loss-of-function mutations in the GLRA1 or GLRB genes, which encode the ?1 and ? glycine receptor (GlyR) subunits, are the major cause...
- Horani S, Stater E, Corringer P, Trudell J, Harris R, Howard R. Ethanol Modulation is Quantitatively Determined by the Transmembrane Domain of Human Î±1 Glycine Receptors. Alcohol Clin Exp Res. 2015;39:962-8 pubmed publisher..This work highlights the relevance of bacterial homologs as valuable model systems for studying ion channel function of human receptors and demonstrates the modularity of these channels across species. ..
- Kling C, Koch M, Saul B, Becker C. The frameshift mutation oscillator (Glra1(spd-ot)) produces a complete loss of glycine receptor alpha1-polypeptide in mouse central nervous system. Neuroscience. 1997;78:411-7 pubmedMice homozygous for the recessive mutation oscillator (Glra1(spd-ot)) suffer from a complex motor disorder leading to death within three weeks after birth...
- Saul B, Schmieden V, Kling C, Mülhardt C, Gass P, Kuhse J, et al. Point mutation of glycine receptor alpha 1 subunit in the spasmodic mouse affects agonist responses. FEBS Lett. 1994;350:71-6 pubmed..As glycine receptor content in spinal cord and native molecular weight appeared unaltered, this suggests that the spasmodic phenotype results from an altered neurotransmitter sensitivity of the mutant alpha 1A52S subunit. ..
- Grudzinska J, Schemm R, Haeger S, Nicke A, Schmalzing G, Betz H, et al. The beta subunit determines the ligand binding properties of synaptic glycine receptors. Neuron. 2005;45:727-39 pubmed..Because the beta subunit anchors GlyRs at synaptic sites, our results have important implications for the biosynthesis, clustering, and pharmacology of synaptic GlyRs. ..
- Grenningloh G, Rienitz A, Schmitt B, Methfessel C, Zensen M, Beyreuther K, et al. The strychnine-binding subunit of the glycine receptor shows homology with nicotinic acetylcholine receptors. Nature. 1987;328:215-20 pubmed..The deduced polypeptide shows significant structural and amino-acid sequence homology with nicotinic acetylcholine receptor proteins, indicating that there is a family of genes encoding neurotransmitter-gated ion channels. ..
- Graham B, Schofield P, Sah P, Callister R. Altered inhibitory synaptic transmission in superficial dorsal horn neurones in spastic and oscillator mice. J Physiol. 2003;551:905-16 pubmed..Furthermore, the spastic mutation results in a compensatory increase in GABAAergic transmission in SFDH neurones, a form of inhibitory synaptic plasticity absent in the oscillator mouse. ..
- Froh M, Thurman R, Wheeler M. Molecular evidence for a glycine-gated chloride channel in macrophages and leukocytes. Am J Physiol Gastrointest Liver Physiol. 2002;283:G856-63 pubmed
- Markstahler U, Kremer E, Kimmina S, Becker K, Richter D. Effects of functional knock-out of alpha 1 glycine-receptors on breathing movements in oscillator mice. Respir Physiol Neurobiol. 2002;130:33-42 pubmedThe effects of a deficiency of glycinergic inhibition deriving from mutations of the glycine-receptor gene Glra1 on the breathing pattern of oscillator mice were studied...
- Bormann J, Rundström N, Betz H, Langosch D. Residues within transmembrane segment M2 determine chloride conductance of glycine receptor homo- and hetero-oligomers. EMBO J. 1994;13:1493 pubmed
- Plested A, Groot Kormelink P, Colquhoun D, Sivilotti L. Single-channel study of the spasmodic mutation alpha1A52S in recombinant rat glycine receptors. J Physiol. 2007;581:51-73 pubmed..This mechanism also predicts accurately the faster decay of synaptic currents that is observed in spasmodic mice. ..
- Ryan S, Buckwalter M, Lynch J, Handford C, Segura L, Shiang R, et al. A missense mutation in the gene encoding the alpha 1 subunit of the inhibitory glycine receptor in the spasmodic mouse. Nat Genet. 1994;7:131-5 pubmed..can be caused by mutations in the gene encoding the alpha 1 subunit of the inhibitory glycine receptor (GLRA1)...
- Mowrey D, Cui T, Jia Y, Ma D, Makhov A, Zhang P, et al. Open-channel structures of the human glycine receptor ?1 full-length transmembrane domain. Structure. 2013;21:1897-904 pubmed publisher..Our structures provide additional templates for identifying potential drug targets in GlyRs and other mammalian pLGICs. ..
- Plappert C, Pilz P, Becker K, Becker C, Schnitzler H. Increased sensitization of acoustic startle response in spasmodic mice with a mutation of the glycine receptor alpha1-subunit gene. Behav Brain Res. 2001;121:57-67 pubmed..Alternatively, glycinergic tonic inhibition of sensitizing structures (e.g. the amygdala) in the wildtype may be diminished in spd/spd mutants, thus leading to a high sensitization level. ..
- Burzomato V, Groot Kormelink P, Sivilotti L, Beato M. Stoichiometry of recombinant heteromeric glycine receptors revealed by a pore-lining region point mutation. Receptors Channels. 2003;9:353-61 pubmed..The magnitude of the leftward shift in the agonist dose-response curve for the two mutant combinations was in agreement with a subunit stoichiometry of 3alpha:2beta. ..
- Hirzel K, Müller U, Latal A, Hülsmann S, Grudzinska J, Seeliger M, et al. Hyperekplexia phenotype of glycine receptor alpha1 subunit mutant mice identifies Zn(2+) as an essential endogenous modulator of glycinergic neurotransmission. Neuron. 2006;52:679-90 pubmed..by producing knockin mice carrying the mutation D80A in the glycine receptor (GlyR) alpha1 subunit gene (Glra1). This substitution selectively eliminates the potentiating effect of Zn(2+) on GlyR currents...