Functional analysis of a de novo GRIN2A missense mutation associated with early-onset epileptic encephalopathy

Nature Communications

Volumn 5, Issue , 2014, Pages

  Yuan, Hongjie ^a   Hansen, Kasper B ^a   Zhang, Jing ^a   Mark Pierson, Tyler ^b,c   Markello, Thomas C ^c   Fajardo, Karin V Fuentes ^c   Holloman, Conisha M ^c   Golas, Gretchen ^c   Adams, David R ^c   Boerkoel, Cornelius F ^c   Gahl, William A ^c   Traynelis, Stephen F ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b CEDARS SINAI MEDICAL CENTER   (United States)

^c NATIONAL HUMAN GENOME RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LEUCINE; MAGNESIUM; METHIONINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2A; PROTON; ZINC; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; N-METHYL D-ASPARTATE RECEPTOR SUBTYPE 2A;

AMINO ACID; BRAIN; ELECTROCHEMICAL METHOD; GENE EXPRESSION; LIGAND; MUTATION; NEUROLOGY; PHENOTYPE; PHYSIOLOGICAL RESPONSE;

ALLOSTERISM; ARTICLE; CHILD; CONTROLLED STUDY; DEVELOPMENTAL DISORDER; ELECTROPHYSIOLOGICAL PROCEDURES; GENETIC ASSOCIATION; HUMAN; IN VITRO STUDY; INTRACTABLE EPILEPSY; LENNOX GASTAUT SYNDROME; MISSENSE MUTATION; PROTEIN ANALYSIS; SENSITIVITY ANALYSIS; AGONISTS; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; CASE REPORT; GENETICS; INFANT; INFANTILE SPASM; MALE; METABOLISM; MOLECULAR GENETICS; NUCLEOTIDE SEQUENCE; STRUCTURE ACTIVITY RELATION;

ALLOSTERIC REGULATION; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; CHILD; DNA MUTATIONAL ANALYSIS; HUMANS; INFANT; MAGNESIUM; MALE; MOLECULAR SEQUENCE DATA; MUTATION, MISSENSE; RECEPTORS, N-METHYL-D-ASPARTATE; SPASMS, INFANTILE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84905913192     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms4251     Document Type: Article

References (71)

1. Akazawa, C., Shigemoto, R., Bessho, Y., Nakanishi, S. & Mizuno, N. Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats. J. Comp. Neurol. 347, 150-160 (1994).
2. Monyer, H., Burnashev, N., Laurie, D. J., Sakmann, B. & Seeburg, P. H. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12, 529-540 (1994).
3. Traynelis, S. F. et al. Glutamate receptor ion channels: structure, regulation, and function. Pharmacol. Rev. 62, 405-496 (2010).
4. Ghasemi, M. & Schachter, S. C. The NMDA receptor complex as a therapeutic target in epilepsy: a review. Epilepsy Behav. 22, 617-640 (2011).
5. Coyle, J. T., Tsai, G. & Goff, D. Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia. Ann. NY Acad. Sci. 1003, 318-327 (2003).
6. Hallett, P. J. & Standaert, D. G. Rationale for and use of NMDA receptor antagonists in Parkinson's disease. Pharmacol. Ther. 102, 155-174 (2004).
7. Arning, L. et al. NR2A and NR2B receptor gene variations modify age at onset in Huntington disease. Neurogenetics 6, 25-28 (2005).
8. Fan, M. M. & Raymond, L. A. N-methyl-D-aspartate (NMDA) receptor function and excitotoxicity in Huntington's disease. Prog. Neurobiol. 81, 272-293 (2007).
9. Saft, C. et al. NMDA receptor gene variations as modifiers in Huntington disease: a replication study. PLoS Curr. 3, RRN1247 (2011).
10. Hamza, T. H. et al. Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee. PLoS Genet. 7, e1002237 (2011).
11. Tarabeux, J. et al. Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia. Transl. Psychiatry 1, e55 (2011).
12. Endele, S. et al. Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes. Nat. Genet. 42, 1021-1026 (2010).
13. Hamdan, F. F. et al. Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am. J. Hum. Genet. 88, 306-316 (2011).
14. de Ligt, J. et al. Diagnostic exome sequencing in persons with severe intellectual disability. N. Engl. J. Med. 367, 1921-1929 (2012).
15. Lemke, J. R. et al. Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes. Nat. Genet. 45, 1067-1072 (2013).
16. Lesca, G. et al. GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction. Nat. Genet. 45, 1061-1066 (2013).
17. Sobolevsky, A. I., Rosconi, M. P. & Gouaux, E. X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor. Nature 462, 745-756 (2009).
18. Heron, S. E. et al. De novo SCN1A mutations in Dravet syndrome and related epileptic encephalopathies are largely of paternal origin. J. Med. Genet. 47, 137-141 (2010).
19. Mastrangelo, M. & Leuzzi, V. Genes of early-onset epileptic encephalopathies: from genotype to phenotype. Pediatr. Neurol. 46, 24-31 (2012).
20. Kohda, K., Wang, Y. & Yuzaki, M. Mutation of a glutamate receptor motif reveals its role in gating and delta2 receptor channel properties. Nat. Neurosci. 3, 315-322 (2000).
21. Jones, K. S., VanDongen, H. M. & VanDongen, A. M. The NMDA receptor M3 segment is a conserved transduction element coupling ligand binding to channel opening. J. Neurosci. 22, 2044-2053 (2002).
22. Sobolevsky, A. I., Rooney, L. & Wollmuth, L. P. Staggering of subunits in NMDAR channels. Biophys. J. 83, 3304-3314 (2002).
23. Yuan, H., Erreger, K., Dravid, S. M. & Traynelis, S. F. Conserved structural and functional control of N-methyl-D-aspartate receptor gating by transmembrane domain M3. J. Biol. Chem. 280, 29708-29716 (2005).
24. Sobolevsky, A. I., Prodromou, M. L., Yelshansky, M. V. & Wollmuth, L. P. Subunit-specific contribution of pore-forming domains to NMDA receptor channel structure and gating. J. Gen. Physiol. 129, 509-525 (2007).
25. Kazi, R. et al. Asynchronous movements prior to pore opening in NMDA receptors. J. Neurosci. 33, 12052-12066 (2013).
26. Regalado, M. P., Villarroel, A. & Lerma, J. Intersubunit cooperativity in the NMDA receptor. Neuron 32, 1085-1096 (2001).
27. Lazzaro, J. T. et al. Functional characterization of CP-465, 022, a selective, noncompetitive AMPA receptor antagonist. Neuropharmacology 42, 143-153 (2002).
28. Ogden, K. K. & Traynelis, S. F. Contribution of the M1 transmembrane helix and pre-M1 region to positive allosteric modulation and gating of N-methyl-D-aspartate receptors. Mol. Pharmacol. 83, 1045-1056 (2013).
29. Nowak, L., Bregestovski, P., Ascher, P., Herbet, A. & Prochiantz, A. Magnesium gates glutamate-activated channels in mouse central neurones. Nature 307, 462-465 (1984).
30. Mayer, M. L., Westbrook, G. L. & Guthrie, P. B. Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature 309, 261-263 (1984).
31. Sakurada, K., Masu, M. & Nakanishi, S. Alteration of Ca2+ permeability and sensitivity to Mg2+ and channel blockers by a single amino acid substitution in the N-methyl-D-aspartate receptor. J. Biol. Chem. 268, 410-415 (1993).
32. Wollmuth, L. P., Kuner, T. & Sakmann, B. Adjacent asparagines in the NR2-subunit of the NMDA receptor channel control the voltage-dependent block by extracellular Mg2+. J. Physiol. 506(Pt 1): 13-32 (1998).
33. Dingledine, R., Borges, K., Bowie, D. & Traynelis, S. F. The glutamate receptor ion channels. Pharmacol. Rev. 51, 7-61 (1999).
34. Lester, R. A., Clements, J. D., Westbrook, G. L. & Jahr, C. E. Channel kinetics determine the time course of NMDA receptor-mediated synaptic currents. Nature 346, 565-567 (1990).
35. Choi, D. W. Glutamate receptors and the induction of excitotoxic neuronal death. Prog. Brain. Res. 100, 47-51 (1994).
36. Rothman, S. M. & Olney, J. W. Excitotoxicity and the NMDA receptor - still lethal after eight years. Trends Neurosci. 18, 57-58 (1995).
37. Talukder, I., Borker, P. & Wollmuth, L. P. Specific sites within the ligand-binding domain and ion channel linkers modulate NMDA receptor gating. J. Neurosci. 30, 11792-11804 (2010).
38. Talukder, I. & Wollmuth, L. P. Local constraints in either the GluN1 or GluN2 subunit equally impair NMDA receptor pore opening. J. Gen. Physiol. 138, 179-194 (2011).
39. Salussolia, C. L., Prodromou, M. L., Borker, P. & Wollmuth, L. P. Arrangement of subunits in functional NMDA receptors. J. Neurosci. 31, 11295-11304 (2011).
40. Weber, Y. G. & Lerche, H. Genetic mechanisms in idiopathic epilepsies. Dev. Med. Child Neurol. 50, 648-654 (2008).
41. Nicita, F. et al. The genetics of monogenic idiopathic epilepsies and epileptic encephalopathies. Seizure 21, 3-11 (2012).
42. Noh, G. J., Jane Tavyev Asher, Y. & Graham, Jr J. M. Clinical review of genetic epileptic encephalopathies. Eur. J. Med. Genet. 55, 281-298 (2012).
43. Tavyev Asher, Y. J. & Scaglia, F. Molecular bases and clinical spectrum of early infantile epileptic encephalopathies. Eur. J. Med. Genet. 55, 299-306 (2012).
44. Carvill, G. L. et al. GRIN2A mutations cause epilepsy-aphasia spectrum disorders. Nat. Genet. 45, 1073-1076 (2013).
45. Pierson, T. M. et al. GRIN2A mutation and early-onset epileptic encephalopathy: personalized therapy with memantine. Ann Clin Transl Neurol. (2014) (in press).
46. Beck, C., Wollmuth, L. P., Seeburg, P. H., Sakmann, B. & Kuner, T. NMDAR channel segments forming the extracellular vestibule inferred from the accessibility of substituted cysteines. Neuron 22, 559-570 (1999).
47. Low, C. M. et al. Molecular determinants of proton-sensitive N-methyl-D-aspartate receptor gating. Mol. Pharmacol. 63, 1212-1222 (2003).
48. Taverna, F. et al. The Lurcher mutation of an alpha-amino-3-hydroxy-5-methyl- 4-isoxazolepropionic acid receptor subunit enhances potency of glutamate and converts an antagonist to an agonist. J. Biol. Chem. 275, 8475-8479 (2000).
49. Sobolevsky, A. I., Beck, C. & Wollmuth, L. P. Molecular rearrangements of the extracellular vestibule in NMDAR channels during gating. Neuron 33, 75-85 (2002).
50. Blanke, M. L. & VanDongen, A. M. The NR1 M3 domain mediates allosteric coupling in the N-methyl-D-aspartate receptor. Mol. Pharmacol. 74, 454-465 (2008).
51. Villarroel, A., Regalado, M. P. & Lerma, J. Glycine-independent NMDA receptor desensitization: localization of structural determinants. Neuron 20, 329-339 (1998).
52. Ogden, K. K. & Traynelis, S. F. New advances in NMDA receptor pharmacology. Trends Pharmacol. Sci. 32, 726-733 (2011).
53. Wei, X. et al. Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nat. Genet. 43, 442-446 (2011).
54. Teer, J. K. et al. Systematic comparison of three genomic enrichment methods for massively parallel DNA sequencing. Genome Res. 20, 1420-1431 (2010).
55. Fuentes Fajardo, K. V. et al. Detecting false-positive signals in exome sequencing. Hum. Mutat. 33, 609-613 (2012).
56. Hedegaard, M., Hansen, K. B., Andersen, K. T., Brauner-Osborne, H. & Traynelis, S. F. Molecular pharmacology of human NMDA receptors. Neurochem. Int. 61, 601-609 (2012).
57. Kniazeff, J. et al. Closed state of both binding domains of homodimeric mGlu receptors is required for full activity. Nat. Struct. Mol. Biol. 11, 706-713 (2004).
58. Jackson, M. R., Nilsson, T. & Peterson, P. A. Retrieval of transmembrane proteins to the endoplasmic reticulum. J. Cell Biol. 121, 317-333 (1993).
59. Jackson, M. R., Nilsson, T. & Peterson, P. A. Identification of a consensus motif for retention of transmembrane proteins in the endoplasmic reticulum. EMBO J. 9, 3153-3162 (1990).
60. Zerangue, N. et al. Analysis of endoplasmic reticulum trafficking signals by combinatorial screening in mammalian cells. Proc. Natl Acad. Sci. USA 98, 2431-2436 (2001).
61. Margeta-Mitrovic, M., Jan, Y. N. & Jan, L. Y. A trafficking checkpoint controls GABA(B) receptor heterodimerization. Neuron 27, 97-106 (2000).
62. Pagano, A. et al. C-terminal interaction is essential for surface trafficking but not for heteromeric assembly of GABA(b) receptors. J. Neurosci. 21, 1189-1202 (2001).
63. Traynelis, S. F., Burgess, M. F., Zheng, F., Lyuboslavsky, P. & Powers, J. L. Control of voltage-independent zinc inhibition of NMDA receptors by the NR1 subunit. J. Neurosci. 18, 6163-6175 (1998).
64. Hansen, K. B. et al. Structural determinants of agonist efficacy at the glutamate binding site of N-methyl-D-aspartate receptors. Mol. Pharmacol. 84, 114-127 (2013).
65. Yuan, H., Hansen, K. B., Vance, K. M., Ogden, K. K. & Traynelis, S. F. Control of NMDA receptor function by the NR2 subunit amino-terminal domain. J. Neurosci. 29, 12045-12058 (2009).
66. Qin, F., Auerbach, A. & Sachs, F. Estimating single-channel kinetic parameters from idealized patch-clamp data containing missed events. Biophys. J. 70, 264-280 (1996).
67. Erreger, K., Dravid, S. M., Banke, T. G., Wyllie, D. J. & Traynelis, S. F. Subunit-specific gating controls rat NR1/NR2A and NR1/NR2B NMDA channel kinetics and synaptic signalling profiles. J. Physiol. 563, 345-358 (2005).
68. Siegler Retchless, B., Gao, W. & Johnson, J. W. A single GluN2 subunit residue controls NMDA receptor channel properties via intersubunit interaction. Nat. Neurosci. 15, 406-413 S401-402 (2012).
69. Lewis, C. A. Ion-concentration dependence of the reversal potential and the single channel conductance of ion channels at the frog neuromuscular junction. J. Physiol. 286, 417-445 (1979).
70. Wollmuth, L. P., Kuner, T. & Sakmann, B. Intracellular Mg2+ interacts with structural determinants of the narrow constriction contributed by the NR1-subunit in the NMDA receptor channel. J. Physiol. 506(Pt 1): 33-52 (1998).
71. Acker, T. M. et al. Mechanism for noncompetitive inhibition by novel GluN2C/D N-methyl-D-aspartate receptor subunit-selective modulators. Mol. Pharmacol. 80, 782-795 (2011).