A novel dominant hyperekplexia mutation Y705C alters trafficking and biochemical properties of the presynaptic glycine transporter GlyT2

Journal of Biological Chemistry

Volumn 287, Issue 34, 2012, Pages 28986-29002

  Giménez, Cecilio ^a,b,c   Pérez Siles, Gonzalo ^a,b   Martínez Villarreal, Jaime ^a,b,c   Arribas González, Esther ^a,c   Jiménez, Esperanza ^a,b,c   Núñe, Enrique ^a,b,c   De Juan Sanz, Jaime ^a,b,c   Fernández Sánchez, Enrique ^a   García Tardón, Noemí ^a,b,c   Ibáñez, Ignacio ^a   Romanelli, Valeria ^b,d   Nevado, Julián ^b,d   James, Victoria M ^e   Topf, Maya ^f   Chung, Seo Kyung ^g   Thomas, Rhys H ^g   Desviat, Lourdes R ^a   Aragón, Carmen ^a,b,c   Zafra, Francisco ^a,b,c   Rees, Mark I ^g   Lapunzina, Pablo ^b,d   Harvey, Robert J ^e   López Corcuera, Beatriz ^a,b,c   more..

^a UNIVERSIDAD AUTÓNOMA DE MADRID   (Spain)

^b CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED DE ENFERMEDADES RARAS CIBERER   (Spain)

^c HOSPITAL UNIVERSITARIO LA PAZ   (Spain)

^d HOSPITAL UNIVERSITARIO LA PAZ IDIPAZ   (Spain)

^e UNIVERSITY OF LONDON   (United Kingdom)

^f UNIVERSITY OF LONDON   (United Kingdom)

^g SWANSEA UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AUDITORY STIMULI; BIOCHEMICAL PROPERTIES; CELL SURFACE EXPRESSION; CLINICAL PRESENTATIONS; DNA SEQUENCING; GLYCINE RECEPTOR; IN-VIVO; INTELLECTUAL DISABILITY; PRESYNAPTIC; SECRETORY PATHWAYS; SURFACE EXPRESSION; TRANS-MEMBRANE DOMAINS; TRANSPORT FUNCTION; UNITED KINGDOM;

ACTIVATION ANALYSIS; CELL MEMBRANES; ELECTROPHYSIOLOGY; GENES; SODIUM;

AMINO ACIDS;

GLYCINE TRANSPORTER 2;

AMINO ACID SUBSTITUTION; ARTICLE; BREATHING DISORDER; CELL SURFACE; CONTROLLED STUDY; DEVELOPMENTAL DISORDER; DNA SEQUENCE; ELECTROPHYSIOLOGY; FACE DYSMORPHIA; FEMALE; GENE MUTATION; GENETIC VARIABILITY; GLYCINE TRANSPORTER 2 GENE; HUMAN; HYPEREKPLEXIA; INTELLECTUAL IMPAIRMENT; MAJOR CLINICAL STUDY; MALE; MUTATOR GENE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; SPAIN; UNITED KINGDOM;

AMINO ACID SUBSTITUTION; ANIMALS; FEMALE; GENES, DOMINANT; GENETIC DISEASES, INBORN; GLYCINE; GLYCINE PLASMA MEMBRANE TRANSPORT PROTEINS; GREAT BRITAIN; HUMANS; ION TRANSPORT; MALE; MUTATION, MISSENSE; NERVE TISSUE PROTEINS; NERVOUS SYSTEM DISEASES; PRESYNAPTIC TERMINALS; PROTEIN TRANSPORT; SPAIN;

EID: 84865220395     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M111.319244     Document Type: Article

References (55)

1. Aragón, C., and López-Corcuera, B. (2003) Structure, function and regulation of glycine neurotransporters. Eur. J. Pharmacol. 479, 249-262
2. Gomeza, J., Hülsmann, S., Ohno, K., Eulenburg, V., Szöke, K., Richter, D., and Betz, H. (2003) Inactivation of the glycine transporter 1 gene discloses vital role of glial glycine uptake in glycinergic inhibition. Neuron 40, 785-796
3. Aragón, C., and López-Corcuera, B. (2005) Glycine transporters. Crucial roles of pharmacological interest revealed by gene deletion. Trends Pharmacol. Sci. 26, 283-286
4. Gomeza, J., Ohno, K., Hülsmann, S., Armsen, W., Eulenburg, V., Richter, D. W., Laube, B., and Betz, H. (2003) Deletion of the mouse glycine transporter 2 results in a hyperekplexia phenotype and postnatal lethality. Neuron 40, 797-806 (Pubitemid 37431039)
5. Gomeza, J., Ohno, K., and Betz, H. (2003) Glycine transporter isoforms in the mammalian central nervous system. Structures, functions and therapeutic promises. Curr. Opin. Drug Discov. Devel. 6, 675-682 (Pubitemid 37287936)
6. Harvey, R. J., Topf, M., Harvey, K., and Rees, M. I. (2008) The genetics of hyperekplexia. More than startle!. Trends Genet. 24, 439-447
7. Andermann, F., Keene, D. L., Andermann, E., and Quesney, L. F. (1980) Startle disease or hyperekplexia. Further delineation of the syndrome. Brain 103, 985-997 (Pubitemid 11209255)
8. Rees, M. I., Harvey, K., Pearce, B. R., Chung, S. K., Duguid, I. C., Thomas, P., Beatty, S., Graham, G. E., Armstrong, L., Shiang, R., Abbott, K. J., Zuberi, S. M., Stephenson, J. B., Owen, M. J., Tijssen, M. A., van den Maagdenberg, A. M., Smart, T. G., Supplisson, S., and Harvey, R. J. (2006) Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease. Nat. Genet. 38, 801-806 (Pubitemid 43980601)
9. Rees, M. I., Harvey, K., Ward, H., White, J. H., Evans, L., Duguid, I. C., Hsu, C. C., Coleman, S. L., Miller, J., Baer, K., Waldvogel, H. J., Gibbon, F., Smart, T. G., Owen, M. J., Harvey, R. J., and Snell, R. G. (2003) Isoform heterogeneity of the human gephyrin gene (GPHN), binding domains to the glycine receptor, and mutation analysis in hyperekplexia. J. Biol. Chem. 278, 24688-24696 (Pubitemid 37548625)
10. 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)
11. 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
12. Eulenburg, V., Becker, K., Gomeza, J., Schmitt, B., Becker, C. M., and Betz, H. (2006) Mutations within the human GLYT2 (SLC6A5) gene associated with hyperekplexia. Biochem. Biophys. Res. Commun. 348, 400-405 (Pubitemid 44188585)
13. Yamashita, A., Singh, S. K., Kawate, T., Jin, Y., and Gouaux, E. (2005) Crystal structure of a bacterial homologue of Na+/Cl--dependent neurotransmitter transporters. Nature 437, 215-223 (Pubitemid 41294479)
14. Haliassos, A., Chomel, J. C., Tesson, L., Baudis, M., Kruh, J., Kaplan, J. C., and Kitzis, A. (1989) Modification of enzymatically amplified DNA for the detection of point mutations. Nucleic Acids Res. 17, 3606 (Pubitemid 19120470)
15. Larkin, M. A., Blackshields, G., Brown, N. P., Chenna, R., McGettigan, P. A., McWilliam, H., Valentin, F., Wallace, I. M., Wilm, A., Lopez, R., Thompson, J. D., Gibson, T. J., and Higgins, D. G. (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23, 2947-2948 (Pubitemid 350162903)
16. Ramensky, V., Bork, P., and Sunyaev, S. (2002) Human non-synonymous SNPs. Server and survey. Nucleic Acids Res. 30, 3894-3900 (Pubitemid 35012462)
17. Sali, A., and Blundell, T. L. (1993) Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol. 234, 779-815 (Pubitemid 24007801)
18. Pérez-Siles, G., Morreale, A., Leo-Macías, A., Pita, G., Ortíz, A. R., Aragón, C., and López-Corcuera, B. (2011) Molecular basis of the differential interaction with lithium of glycine transporters GLYT1 and GLYT2. J. Neurochem. 118, 195-204
19. Fornés, A., Núñez, E., Aragón, C., and López-Corcuera, B. (2004) The second intracellular loop of the glycine transporter 2 contains crucial residues for glycine transport and phorbol ester-induced regulation. J. Biol. Chem. 279, 22934-22943
20. Pérez-Siles, G., Núñez, E., Morreale, A., Jiménez, E., Leo-Macías, A., Pita, G., Cherubino, F., Sangaletti, R., Bossi, E., Ortíz, A. R., Aragón, C., and López- Corcuera, B. (2012) An aspartate residue in the external vestibule of GLYT2 (glycine transporter 2) controls cation access and transport coupling. Biochem. J. 442, 323-334
21. Jiménez, E., Zafra, F., Pérez-Sen, R., Delicado, E. G., Miras-Portugal, M. T., Aragón, C., and López-Corcuera, B. (2011) P2Y purinergic regulation of the glycine neurotransmitter transporters. J. Biol. Chem. 286, 10712-10724
22. Núñez, E., Pérez-Siles, G., Rodenstein, L., Alonso-Torres, P., Zafra, F., Jiménez, E., Aragón, C., and López-Corcuera, B. (2009) Subcellular localization of the neuronal glycine transporter GLYT2 in brainstem. Traffic 10, 829-843
23. Fornés, A., Núñez, E., Alonso-Torres, P., Aragón, C., and López-Corcuera, B. (2008) Trafficking properties and activity regulation of the neuronal glycine transporter GLYT2 by protein kinase C. Biochem. J. 412, 495-506
24. de Juan-Sanz, J., Zafra, F., López-Corcuera, B., and Aragón, C. (2011) Endocytosis of the neuronal glycine transporter GLYT2. Role of membrane rafts and protein kinase C-dependent ubiquitination. Traffic 12, 1850-1867
25. López-Corcuera, B., Martínez-Maza, R., Núñez, E., Roux, M., Supplisson, S., and Aragón, C. (1998) Differential properties of two stably expressed brain-specific glycine transporters. J. Neurochem. 71, 2211-2219
26. Martínez-Maza, R., Poyatos, I., López-Corcuera, B., Núñez, E., Giménez, C., Zafra, F., and Aragón, C. (2001) The role of N-glycosylation in transport to the plasma membrane and sorting of the neuronal glycine transporter GLYT2. J. Biol. Chem. 276, 2168-2173
27. Dunn, S. M., Conti-Tronconi, B. M., and Raftery, M. A. (1986) Acetylcholine receptor dimers are stabilized by extracellular disulfide bonding. Biochem. Biophys. Res. Commun. 139, 830-837 (Pubitemid 16002499)
28. Hepojoki, J., Strandin, T., Vaheri, A., and Lankinen, H. (2010) Interactions and oligomerization of hantavirus glycoproteins. J. Virol. 84, 227-242
29. Petäjä-Repo, U. E., Hogue, M., Bhalla, S., Laperrière, A., Morello, J. P., and Bouvier, M. (2002) Ligands act as pharmacological chaperones and increase the efficiency of delta opioid receptor maturation. EMBO J. 21, 1628-1637
30. Chen, J. G., Liu-Chen, S., and Rudnick, G. (1997) External cysteine residues in the serotonin transporter. Biochemistry 36, 1479-1486 (Pubitemid 27074972)
31. Chen, R., Wei, H., Hill, E. R., Chen, L., Jiang, L., Han, D. D., and Gu, H. H. (2007) Direct evidence that two cysteines in the dopamine transporter form a disulfide bond. Mol. Cell Biochem. 298, 41-48 (Pubitemid 46605282)
32. Forlani, G., Bossi, E., Ghirardelli, R., Giovannardi, S., Binda, F., Bonadiman, L., Ielmini, L., and Peres, A. (2001) Mutation K448E in the external loop 5 of rat GABA transporter rGAT1 induces pH sensitivity and alters substrate interactions. J. Physiol. 536, 479-494 (Pubitemid 32976129)
33. Grossman, T. R., and Nelson, N. (2003) Effect of sodium lithium and proton concentrations on the electrophysiological properties of the four mouse GABA transporters expressed in Xenopus oocytes. Neurochem. Int. 43, 431-443 (Pubitemid 36561297)
34. Lynch, J. W., Jacques, P., Pierce, K. D., and Schofield, P. R. (1998) Zinc potentiation of the glycine receptor chloride channel is mediated by allosteric pathways. J. Neurochem. 71, 2159-2168 (Pubitemid 28491574)
35. Hirzel, K., Müller, U., Latal, A. T., Hülsmann, S., Grudzinska, J., Seeliger, M. W., Betz, H., and Laube, B. (2006) Hyperekplexia phenotype of glycine receptor α1 subunit mutant mice identifies Zn2+ as an essential endogenous modulator of glycinergic neurotransmission. Neuron 52, 679-690
36. Tóth, K. (2011) Zinc in neurotransmission. Annu. Rev. Nutr. 31, 139-153
37. Laube, B. (2002) Potentiation of inhibitory glycinergic neurotransmission by Zn2+. A synergistic interplay between presynaptic P2X2 and postsynaptic glycine receptors. Eur. J. Neurosci. 16, 1025-1036
38. Ju, P., Aubrey, K. R., and Vandenberg, R. J. (2004) Zn2+ inhibits glycine transport by glycine transporter subtype 1b. J. Biol. Chem. 279, 22983-22991 (Pubitemid 38685600)
39. Chu, X. P., Wemmie, J. A., Wang, W. Z., Zhu, X. M., Saugstad, J. A., Price, M. P., Simon, R. P., and Xiong, Z. G. (2004) Subunit-dependent high-affinity zinc inhibition of acid-sensing ion channels. J. Neurosci. 24, 8678-8689 (Pubitemid 39362963)
40. Baron, A., Voilley, N., Lazdunski, M., and Lingueglia, E. (2008) Acid sensing ion channels in dorsal spinal cord neurons. J. Neurosci. 28, 1498-1508 (Pubitemid 351231523)
41. Chen, J., Myerburg, M. M., Passero, C. J., Winarski, K. L., and Sheng, S. (2011) External Cu2+ inhibits human epithelial Na+ channels by binding at a subunit interface of extracellular domains. J. Biol. Chem. 286, 27436-27446
42. Dudev, T., and Lim, C. (2002) Factors governing the protonation state of cysteines in proteins. An ab initio/CDM study. J. Am. Chem. Soc. 124, 6759-6766 (Pubitemid 34602669)
43. Leskelä, T. T., Markkanen, P. M., Alahuhta, I. A., Tuusa, J. T., and Petäjä-Repo, U. E. (2009) Phe27Cys polymorphism alters the maturation and subcellular localization of the human delta opioid receptor. Traffic 10, 116-129
44. Schülein, R., Zühlke, K., Krause, G., and Rosenthal, W. (2001) Functional rescue of the nephrogenic diabetes insipidus-causing vasopressin V2 receptor mutants G185C and R202C by a second site suppressor mutation. J. Biol. Chem. 276, 8384-8392
45. Williams, S. E., Reed, A. A., Galvanovskis, J., Antignac, C., Goodship, T., Karet, F. E., Kotanko, P., Lhotta, K., Morinière, V., Williams, P., Wong, W., Rorsman, P., and Thakker, R. V. (2009) Uromodulin mutations causing familial juvenile hyperuricaemic nephropathy lead to protein maturation defects and retention in the endoplasmic reticulum. Hum. Mol. Genet. 18, 2963-2974
46. Krishnamurthy, H., and Gouaux, E. (2012) X-ray structures of LeuT in substrate-free outward-open and apo inward-open states. Nature 481, 469-474
47. Bartholomäus, I., Milan-Lobo, L., Nicke, A., Dutertre, S., Hastrup, H., Jha, A., Gether, U., Sitte, H. H., Betz, H., and Eulenburg, V. (2008) Glycine transporter dimers. Evidence for occurrence in the plasma membrane. J. Biol. Chem. 283, 10978-10991
48. Pace, C. N., Grimsley, G. R., and Scholtz, J. M. (2009) Protein ionizable groups. pK values and their contribution to protein stability and solubility. J. Biol. Chem. 284, 13285-13289
49. Chen, Z., Dillon, G. H., and Huang, R. (2004) Molecular determinants of proton modulation of glycine receptors. J. Biol. Chem. 279, 876-883 (Pubitemid 38082607)
50. Aubrey, K. R., Mitrovic, A. D., and Vandenberg, R. J. (2000) Molecular basis for proton regulation of glycine transport by glycine transporter subtype 1b. Mol. Pharmacol. 58, 129-135 (Pubitemid 30452535)
51. Krishtal, O. (2003) The ASICs. Signaling molecules? Modulators? Trends Neurosci. 26, 477-483
52. Jasti, J., Furukawa, H., Gonzales, E. B., and Gouaux, E. (2007) Structure of acid-sensing ion channel 1 at 1.9 Å resolution and low pH. Nature 449, 316-323 (Pubitemid 47443482)
53. Krishtal, O. A., Osipchuk, Y. V., Shelest, T. N., and Smirnoff, S. V. (1987) Rapid extracellular pH transients related to synaptic transmission in rat hippocampal slices. Brain Res. 436, 352-356 (Pubitemid 18003573)
54. Li, Y. F., Wu, L. J., Li, Y., Xu, L., and Xu, T. L. (2003) Mechanisms of H+ modulation of glycinergic response in rat sacral dorsal commissural neurons. J. Physiol. 552, 73-87 (Pubitemid 37265469)
55. Smart, T. G., Hosie, A. M., and Miller, P. S. (2004) Zn 2+ ions. Modulators of excitatory and inhibitory synaptic activity. Neuroscientist 10, 432-442 (Pubitemid 39244580)