Disturbed neuronal er-golgi sorting of unassembled glycine receptors suggests altered subcellular processing is a cause of human hyperekplexia

Journal of Neuroscience

Volumn 35, Issue 1, 2015, Pages 422-437

  Schaefer, Natascha ^a   Kluck, Christoph J ^b   Price, Kerry L ^c   Meiselbach, Heike ^b   Vornberger, Nadine ^a   Schwarzinger, Stephan ^d   Hartmann, Stephanie ^b   Langlhofer, Georg ^a   Schulz, Solveig ^e   Schlegel, Nadja ^e   Brockmann, Knut ^f   Lynch, Bryan ^g   Becker, Cord Michael ^b   Lummis, Sarah C R ^c   Villmann, Carmen ^a  

^a UNIVERSITY OF WÜRZBURG   (Germany)

^b UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^c UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^d UNIVERSITY OF BAYREUTH   (Germany)

^e JENA UNIVERSITY HOSPITAL   (Germany)

^f UNIVERSITY OF GÖTTINGEN   (Germany)

^g CHILDREN S UNIVERSITY HOSPITAL   (Ireland)

Author keywords

Assembly; Biogenesis; Glycine receptor; Human hyperekplexia; Rescue of function; Subcompartimentalization

Indexed keywords

CALNEXIN; GENOMIC DNA; GLYCINE RECEPTOR; GLYCINE RECEPTOR ALPHA 1; ION CHANNEL; PROTEIN VARIANT; UNCLASSIFIED DRUG; GLYCINE RECEPTOR ALPHA1;

ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; BIOTINYLATION; CARBOXY TERMINAL SEQUENCE; CASE REPORT; CELL MEMBRANE; CELL MIGRATION; CHILD; CIRCULAR DICHROISM; DNA SEQUENCE; ENDOPLASMIC RETICULUM; FEMALE; GENE MUTATION; GENETIC TRANSFECTION; GOLGI COMPLEX; HIPPOCAMPUS; HUMAN; HUMAN CELL; HYPEREKPLEXIA; IMMUNOCYTOCHEMISTRY; IMMUNOPRECIPITATION; MALE; MOUSE; NERVE CELL; NERVE POTENTIAL; NONHUMAN; PATCH CLAMP TECHNIQUE; PHENOTYPE; PRESCHOOL CHILD; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN GLYCOSYLATION; PROTEIN LOCALIZATION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; PROTEIN SECONDARY STRUCTURE; RECEPTOR BINDING ASSAY; SEIZURE; SITE DIRECTED MUTAGENESIS; SUCROSE DENSITY GRADIENT CENTRIFUGATION; AMINO ACID SEQUENCE; ANIMAL; BIOSYNTHESIS; CHEMISTRY; CHLOROCEBUS AETHIOPS; COS 1 CELL LINE; GENETICS; HEK293 CELL LINE; INFANT; INTRACELLULAR SPACE; METABOLISM; MOLECULAR GENETICS; PEDIGREE; PROTEIN TERTIARY STRUCTURE; STIFF-PERSON SYNDROME;

AMINO ACID SEQUENCE; ANIMALS; CERCOPITHECUS AETHIOPS; CHILD; COS CELLS; ENDOPLASMIC RETICULUM; FEMALE; GOLGI APPARATUS; HEK293 CELLS; HUMANS; INFANT; INTRACELLULAR SPACE; MALE; MICE; MOLECULAR SEQUENCE DATA; NEURONS; PEDIGREE; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, GLYCINE; STIFF-PERSON SYNDROME;

EID: 84920545134     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.1509-14.2015     Document Type: Article

References (40)

1. 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, et al. (2013) New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms. J Biol Chem 288:33745–33759.
2. Bode A, Lynch JW (2013) Analysis of hyperekplexia mutations identifies transmembrane domain rearrangements that mediate glycine receptor activation. J Biol Chem 288:33760–33771.
3. Bode A, Lynch JW (2014) The impact of human hyperekplexia mutations on glycine receptor structure and function. Mol Brain 7:2.
4. Brams M, Pandya A, Kuzmin D, van Elk R, Krijnen L, Yakel JL, Tsetlin V, Smit AB, Ulens C (2011) A structural and mutagenic blueprint for molecular recognition ofstrychnine and d-tubocurarinebydifferent cys-loop receptors. PLoS Biol 9:e1001034.
5. Breitinger U, Breitinger HG, Bauer F, Fahmy K, Glockenhammer D, Becker CM (2004) Conserved high affinity ligand binding and membrane association in the native and refolded extracellular domain of the human glycine receptor alpha1-subunit. J Biol Chem 279:1627–1636.
6. Brejc K, van Dijk WJ, Klaassen RV, Schuurmans M, van Der Oost J, Smit AB, Sixma TK (2001) Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors. Nature 411:269–276.
7. 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, Ander-mann E, Thomas RH, Harvey RJ, et al. (2010) Pathophysiological mechanisms of dominant and recessive GLRA1 mutations in hyperekplexia. J Neurosci 30:9612–9620.
8. 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, et al. (2013) GLRB is the third major gene of effect in hyperek-plexia. Hum Mol Genet 22:927–940.
9. Conti E, Izaurralde E (2005) Nonsense-mediated mRNA decay: molecular insights and mechanistic variations across species. Curr Opin Cell Biol 17:316–325.
10. Coto E, Armenta D, Espinosa R, Argente J, Castro MG, Alvarez V (2005) Recessive hyperekplexia due to a new mutation (R100H) in the GLRA1 gene. Mov Disord 20:1626–1629.
11. Gotti C, Hanke W, Schlue WR, Briscini L, Moretti M, Clementi F (1992) A functional alpha-bungarotoxin receptor is present in chick cerebellum: purification and characterization. Neuroscience 50:117–127.
12. Griffon N, Büttner C, Nicke A, Kuhse J, Schmalzing G, Betz H (1999) Molecular determinants of glycine receptor subunit assembly. EMBO J 18: 4711–4721.
13. Grudzinska J, Schemm R, Haeger S, Nicke A, Schmalzing G, Betz H, Laube B (2005) The beta subunit determines the ligand binding properties of synaptic glycine receptors. Neuron 45:727–739.
14. Haeger S, Kuzmin D, Detro-Dassen S, Lang N, Kilb M, Tsetlin V, Betz H, Laube B, Schmalzing G (2010) An intramembrane aromatic network determines pentameric assembly of Cys-loop receptors. Nat Struct Mol Biol 17:90–98.
15. Hibbs RE, Gouaux E (2011) Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature 474:54–60.
16. Hibbs RE, Sulzenbacher G, Shi J, Talley TT, Conrod S, Kem WR, Taylor P, Marchot P, Bourne Y (2009) Structural determinants for interaction of partial agonists with acetylcholine binding protein and neuronal alpha7 nicotinic acetylcholine receptor. EMBO J 28:3040–3051.
17. Hooft RW, Vriend G, Sander C, Abola EE (1996) Errors in protein structures. Nature 381:272.
18. James VM, Bode A, Chung SK, Gill JL, Nielsen M, Cowan FM, Vujic M, Thomas RH, Rees MI, Harvey K, Keramidas A, Topf M, Ginjaar I, Lynch JW, Harvey RJ (2013) Novel missense mutations in the glycine receptor beta subunit gene (GLRB) in startle disease. Neurobiol Dis 52:137–149.
19. Kling C, Koch M, Saul B, Becker CM (1997) The frameshift mutation oscillator (Glra1(spd-ot)) produces acomplete lossofglycine receptor alpha1-polypeptide in mouse central nervous system. Neuroscience 78:411–417.
20. Lecker SH, Goldberg AL, Mitch WE (2006) Protein degradation by the ubiquitin-proteasome pathway in normal and disease states. J Am Soc Nephrol 17:1807–1819.
21. Mazzo F, Pistillo F, Grazioso G, Clementi F, Borgese N, Gotti C, Colombo SF (2013) Nicotine-modulated subunit stoichiometry affects stability and trafficking ofalpha3beta4 nicotinic receptor. J Neurosci 33:12316–12328.
22. Pless SA, Millen KS, Hanek AP, Lynch JW, Lester HA, Lummis SC, Dougherty DA (2008) A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue. J Neurosci 28:10937–10942.
23. Pless SA, Hanek AP, Price KL, Lynch JW, Lester HA, Dougherty DA, Lummis SC (2011) A cation-pi interaction at a phenylalanine residue in the gly-cine receptor binding site is conserved for different agonists. Mol Pharmacol 79:742–748.
24. Raussens V, Ruysschaert JM, Goormaghtigh E (2003) Protein concentration is not an absolute prerequisite for the determination of secondary structure from circular dichroism spectra: a new scaling method. Anal Biochem 319:114–121.
25. Raussens V, Ruysschaert JM, Goormaghtigh E (2006) Erratum to “Protein concentration is not an absolute prerequisite for the determination of secondary structure from circular dichroism spectra: A new scaling method”. Anal Biochem 359:150.
26. 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, Sup-plisson S, Harvey RJ (2006) Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease. Nat Genet 38:801–806.
27. Riganti L, Matteoni C, Di Angelantonio S, Nistri A, Gaimarri A, Sparatore F, Canu-Boido C, Clementi F, Gotti C (2005) Long-term exposure to the new nicotinic antagonist 1,2-bisN-cytisinylethane upregulates nicotinic receptor subtypes of SH-SY5Y human neuroblastoma cells. Br J Pharmacol 146:1096–1109.
28. Ross AF, Green WN, Hartman DS, Claudio T (1991) Efficiency of acetyl-choline receptor subunit assembly and its regulation by cAMP. J Cell Biol 113:623–636.
29. Sadtler S, Laube B, Lashub A, Nicke A, Betz H, Schmalzing G (2003) A basic cluster determines topology of the cytoplasmic M3–M4 loop of the glycine receptor alpha1 subunit. J Biol Chem 278:16782–16790.
30. Sánchez R, Sali A (2000) Comparative protein structure modeling. Introduction and practical examples with modeller. Methods Mol Biol 143:97–129.
31. Schaefer N, Langlhofer G, Kluck CJ, Villmann C (2013) Glycine receptor mouse mutants: model systems for human hyperekplexia. BrJ Pharmacol 170:933–952.
32. Seeger C, Christopeit T, Fuchs K, Grote K, Sieghart W, Du H (2012) His-taminergic pharmacology of homo-oligomeric beta3 gamma-aminobutyric acid type A receptors characterized by surface plasmon resonance biosensor technology. Biochem Pharmacol 84:341–351.
33. Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W:improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680.
34. Tsai CH, Chang FC, Su YC, Tsai FJ, Lu MK, Lee CC, Kuo CC, Yang YW, Lu CS (2004) Two novel mutations of the glycine receptor gene in a Taiwanese hyper-ekplexia family. Neurology 63:893–896.
35. Unterer B, Becker CM, Villmann C (2012) The importance of TM3–4 loop subdomains for functional reconstitution of glycine receptors by independent domains. J Biol Chem 287:39205–39215.
36. Vergouwe MN, Tijssen MA, Peters AC, Wielaard R, Frants RR (1999) Hyperekplexia phenotype due to compound heterozygosity for GLRA1 gene mutations. Ann Neurol 46:634–638.
37. Villmann C, Oertel J, Melzer N, Becker CM (2009a) Recessive hyperek-plexia mutations of the glycine receptor alpha1 subunit affect cell surface integration and stability. J Neurochem 111:837–847.
38. Villmann C, Oertel J, Ma-Högemeier ZL, Hollmann M, Sprengel R, Becker K, Breitinger HG, Becker CM (2009b) Functional complementation of Glra1(spd-ot), a glycine receptor subunit mutant, by independently expressed C-terminal domains. J Neurosci 29:2440–2452.
39. Vogel N, Kluck CJ, Melzer N, Schwarzinger S, Breitinger U, Seeber S, Becker CM (2009) Mapping of disulfide bonds within the amino-terminal extracellular domain of the inhibitory glycine receptor. J Biol Chem 284: 36128–36136.
40. Wanamaker CP, Green WN (2007) Endoplasmic reticulum chaperones stabilize nicotinic receptor subunits and regulate receptor assembly. J Biol Chem 282:31113–31123.