Glycine receptor, alpha 1 explained

Glycine receptor subunit alpha-1 is a protein that in humans is encoded by the GLRA1 gene.^{[1] [2]}

Function

The inhibitory glycine receptor mediates postsynaptic inhibition in the spinal cord and other regions of the central nervous system. It is a pentameric receptor composed solely of alpha subunits. The GLRB gene encodes the alpha subunit of the receptor.^[3]

Clinical significance

Mutations in the gene have been associated with hyperekplexia, a neurologic syndrome associated with an exaggerated startle reaction.^{[4] [5]}

See also

• Glycine receptor
• Stiff person syndrome
• Hyperekplexia

Further reading

• Ruiz-Gómez A, Vaello ML, Valdivieso F, Mayor F . Phosphorylation of the 48-kDa subunit of the glycine receptor by protein kinase C . J. Biol. Chem. . 266 . 1 . 559–566 . 1991 . 10.1016/S0021-9258(18)52472-8 . 1845981 . free .
• Grenningloh G, Schmieden V, Schofield PR, Seeburg PH, Siddique T, Mohandas TK, Becker CM, Betz H . Alpha subunit variants of the human glycine receptor: primary structures, functional expression and chromosomal localization of the corresponding genes . EMBO J. . 9 . 3 . 771–776 . 1990 . 2155780 . 551735 . 10.1002/j.1460-2075.1990.tb08172.x.
• Langosch D, Herbold A, Schmieden V, Borman J, Kirsch J . Importance of Arg-219 for correct biogenesis of alpha 1 homooligomeric glycine receptors . FEBS Lett. . 336 . 3 . 540–544 . 1994 . 7506679 . 10.1016/0014-5793(93)80872-R . 84795107 . free .
• 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. . 38 . 1 . 85–91 . 1995 . 7611730 . 10.1002/ana.410380115 . 22129217 .
• Baker E, Sutherland GR, Schofield PR . Grant Robert Sutherland . Localization of the glycine receptor alpha 1 subunit gene (GLRA1) to chromosome 5q32 by FISH . Genomics . 22 . 2 . 491–493 . 1995 . 7806244 . 10.1006/geno.1994.1419 .
• 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. . 3 . 12 . 2175–2179 . 1995 . 7881416 . 10.1093/hmg/3.12.2175 .
• Ryan SG, Buckwalter MS, Lynch JW, Handford CA, Segura L, Shiang R, Wasmuth JJ, Camper SA, Schofield P, O'Connell P . A missense mutation in the gene encoding the alpha 1 subunit of the inhibitory glycine receptor in the spasmodic mouse . Nat. Genet. . 7 . 2 . 131–135 . 1994 . 7920629 . 10.1038/ng0694-131 . 32946709 .
• Langosch D, Laube B, Rundström N, Schmieden V, Bormann J, Betz H . Decreased agonist affinity and chloride conductance of mutant glycine receptors associated with human hereditary hyperekplexia . EMBO J. . 13 . 18 . 4223–4228 . 1994 . 7925268 . 395349 . 10.1002/j.1460-2075.1994.tb06742.x.
• Schorderet DF, Pescia G, Bernasconi A, Regli F . An additional family with Startle disease and a G1192A mutation at the alpha 1 subunit of the inhibitory glycine receptor gene . Hum. Mol. Genet. . 3 . 7 . 1201 . 1995 . 7981700 . 10.1093/hmg/3.7.1201 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–174 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• 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. . 13 . 6 . 1493 . 1994 . 8137830 . 394970 . 10.1002/j.1460-2075.1994.tb06405.x.
• Milani N, Dalprá 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. . 58 . 2 . 420–422 . 1996 . 8571969 . 1914546 .
• Brune W, Weber RG, Saul B, von Knebel Doeberitz M, Grond-Ginsbach C, Kellerman K, Meinck HM, Becker CM . A GLRA1 null mutation in recessive hyperekplexia challenges the functional role of glycine receptors . Am. J. Hum. Genet. . 58 . 5 . 989–997 . 1996 . 8651283 . 1914607 .
• 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. . 33 . 5 . 435–436 . 1996 . 8733061 . 1050620 . 10.1136/jmg.33.5.435 .
• Monani U, Burghes AH . Structure of the human alpha 2 subunit gene of the glycine receptor--use of vectorette and Alu-exon PCR . Genome Res. . 6 . 12 . 1200–1206 . 1997 . 8973915 . 10.1101/gr.6.12.1200 . free .
• Seri M, Bolino A, Galietta LJ, Lerone M, Silengo M, Romeo G . Startle disease in an Italian family by mutation (K276E): The alpha-subunit of the inhibiting glycine receptor . Hum. Mutat. . 9 . 2 . 185–187 . 1997 . 9067762 . 10.1002/(SICI)1098-1004(1997)9:2<185::AID-HUMU14>3.0.CO;2-Z . 38078893 . free .
• Vergouwe MN, Tijssen MA, Shiang R, van Dijk JG, al Shahwan S, Ophoff RA, Frants RR . Hyperekplexia-like syndromes without mutations in the GLRA1 gene . Clinical Neurology and Neurosurgery . 99 . 3 . 172–178 . 1998 . 9350397 . 10.1016/S0303-8467(97)00022-X . 43274005 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–156 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .

Notes and References

1. Ryan SG, Sherman SL, Terry JC, Sparkes RS, Torres MC, Mackey RW . Startle disease, or hyperekplexia: response to clonazepam and assignment of the gene (STHE) to chromosome 5q by linkage analysis . Ann Neurol . 31 . 6 . 663–668 . Sep 1992 . 1355335 . 10.1002/ana.410310615 . 28879043 .
2. Shiang R, Ryan SG, Zhu YZ, Hahn AF, O'Connell P, Wasmuth JJ . Mutations in the alpha 1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia . Nat Genet . 5 . 4 . 351–358 . Mar 1994 . 8298642 . 10.1038/ng1293-351 . 21410824 .
3. Web site: Entrez Gene: GLRA1 glycine receptor, alpha 1 (startle disease/hyperekplexia, stiff man syndrome).
4. Tijssen MA, Shiang R, van Deutekom J, Boerman RH, Wasmuth JJ, Sandkuijl LA, Frants RR, Padberg GW . Molecular genetic reevaluation of the Dutch hyperekplexia family . Arch. Neurol. . 52 . 6 . 578–582 . June 1995 . 7763205 . 10.1001/archneur.1995.00540300052012 . 2066/20657 . 14067463 . free .
5. Zhou L, Chillag KL, Nigro MA . Hyperekplexia: a treatable neurogenetic disease . Brain Dev. . 24 . 7 . 669–674 . October 2002 . 12427512 . 10.1016/S0387-7604(02)00095-5 . 40864297 .