Abnormal subcellular localization of GABA A receptor subunits in schizophrenia brain

Translational Psychiatry

Volumn 5, Issue , 2015, Pages

  Mueller, T M ^a   Remedies, C E ^a,b   Haroutunian, V ^c   Meador Woodruff, J H ^a  

^a UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^b UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^c MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR ALPHA1; 4 AMINOBUTYRIC ACID A RECEPTOR ALPHA2; 4 AMINOBUTYRIC ACID A RECEPTOR BETA1; 4 AMINOBUTYRIC ACID A RECEPTOR BETA2; 4 AMINOBUTYRIC ACID A RECEPTOR GAMMA2; ISOPROTEIN; 4 AMINOBUTYRIC ACID A RECEPTOR; 4 AMINOBUTYRIC ACID B RECEPTOR; GABBR2 PROTEIN, HUMAN; GABRA1 PROTEIN, HUMAN; GABRB1 PROTEIN, HUMAN; GABRB2 PROTEIN, HUMAN;

AGED; ARTICLE; CELL FRACTIONATION; CLINICAL ARTICLE; CONTROLLED STUDY; ENDOPLASMIC RETICULUM; FEMALE; HUMAN; HUMAN TISSUE; MALE; MOLECULAR PATHOLOGY; NEUROPATHOLOGY; PROTEIN ASSEMBLY; PROTEIN EXPRESSION; PROTEIN GLYCOSYLATION; PROTEIN LOCALIZATION; PROTEIN TRANSPORT; SCHIZOPHRENIA; SYNAPSE; WESTERN BLOTTING; BRAIN; CASE CONTROL STUDY; CHEMISTRY; GLYCOSYLATION; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; TEMPORAL LOBE;

AGED; BLOTTING, WESTERN; BRAIN; CASE-CONTROL STUDIES; ENDOPLASMIC RETICULUM; FEMALE; GLYCOSYLATION; HUMANS; MALE; RECEPTORS, GABA-A; RECEPTORS, GABA-B; SCHIZOPHRENIA; SUBCELLULAR FRACTIONS; SYNAPSES; TEMPORAL LOBE;

EID: 84938587842     PISSN: None     EISSN: 21583188     Source Type: Journal    
DOI: 10.1038/tp.2015.102     Document Type: Article

References (95)

1. Gonzalez-Burgos G, Fish KN, Lewis DA. GABA neuron alterations, cortical circuit dysfunction and cognitive deficits in schizophrenia. Neural Plast 2011; 2011: 723184.
2. Lewis DA, Hashimoto T, Volk DW. Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci 2005; 6: 312-324.
3. Lewis DA, Curley AA, Glausier JR, Volk DW. Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia. Trends Neurosci 2012; 35: 57-67.
4. Uhlhaas PJ, Singer W. Neural synchrony in brain disorders: relevance for cognitive dysfunctions and pathophysiology. Neuron 2006; 52: 155-168.
5. Nakazawa K, Zsiros V, Jiang Z, Nakao K, Kolata S, Zhang S et al. GABAergic interneuron origin of schizophrenia pathophysiology. Neuropharmacology 2012; 62: 1574-1583.
6. Charych EI, Liu F, Moss SJ, Brandon NJ. GABAA receptors and their associated proteins: Implications in the etiology and treatment of schizophrenia and related disorders. Neuropharmacology 2009; 57: 481-495.
7. Lewis DA, Pierri JN, Volk DW, Melchitzky DS, Woo T-UW. Altered GABA neurotransmission and prefrontal cortical dysfunction in schizophrenia. Biol Psychiatry 1999; 46: 616-626.
8. Volk DW, Lewis DA. Early developmental disturbances of cortical inhibitory neurons: contribution to cognitive deficits in schizophrenia. Schizophr Bull 2014; 40: 952-957.
9. Curley AA, Lewis DA. Cortical basket cell dysfunction in schizophrenia. J Physiol 2012; 590(Pt 4): 715-724.
10. Benes FM. Emerging principles of altered neural circuitry in schizophrenia. Brain Res Rev 2000; 31: 251-269.
11. Green MF, Kern RS, Braff DL, Mintz J. Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the 'right stuff'? Schizophr Bull 2000; 26: 119-136.
12. Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 1996; 153: 321-330.
13. Akbarian S, Kim JJ, Potkin SG, Hagman JO, Tafazzoli A, Bunney WE et al. Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch Gen Psychiatry 1995; 52: 258-266.
14. Guidotti AR, Auta J, Davis JM, Gerevini VD, Dwivedi Y, Grayson DR et al. Decrease in reelin and glutamic acid decarboxylase 67 (GAD 67 ) expression in schizophrenia and bipolar disorder. Arch Gen Psychiatry 2000; 57: 1061-1069.
15. Hashimoto T, Arion D, Unger T, Maldonado-Avilés JG, Morris HM, Volk DW et al. Alterations in GABA-related transcriptome in the dorsolateral prefrontal cortex of subjects with schizophrenia. Mol Psychiatry 2008; 13: 147-161.
16. Hashimoto T, Volk DW, Eggan SM, Mirnics K, Pierri JN, Sun Z et al. Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia. J Neurosci 2003; 23: 6315-6326.
17. Hashimoto T, Bazmi HH, Mirnics K, Wu Q, Sampson AR, Lewis DA. Conserved regional patterns of GABA-related transcript expression in the neocortex of subjects with schizophrenia. Am J Psychiatry 2008; 165: 479-489.
18. Hyde TM, Lipska BK, Ali T, Mathew SV, Law AJ, Metitiri OE et al. Expression of GABA signaling molecules KCC2, NKCC1, and GAD1 in cortical development and schizophrenia. J Neurosci 2011; 31: 11088-11095.
19. Benes FM, Lim B, Matzilevich D, Walsh JP, Subburaju S, Minns M. Regulation of the GABA cell phenotype in hippocampus of schizophrenics and bipolars. Proc Natl Acad Sci USA 2007; 104: 10164-10169.
20. Volk DW, Austin MC, Pierri JN, Sampson AR, Lewis DA. Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyric acid neurons in subjects with schizophrenia. Arch Gen Psychiatry 2000; 57: 237-245.
21. Mirnics K, Middleton FA, Marquez A, Lewis DA, Levitt P. Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex. Neuron 2000; 28: 53-67.
22. Gonzalez-Burgos G, Lewis DA. GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia. Schizophr Bull 2008; 34: 944-961.
23. Benes FM, Berretta S. GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 2001; 25: 1-27.
24. Mulligan MK, Wang X, Adler AL, Mozhui K, Lu L, Williams RW. Complex control of GABA(A) receptor subunit mRNA expression: variation, covariation, and genetic regulation. PLoS One 2012; 7: e34586.
25. Sieghart W. Structure and pharmacology of gamma-aminobutyric acidA receptor subtypes. Pharmacol Rev 1995; 47: 181-234.
26. McKernan RM, Whiting PJ. Which GABAA-receptor subtypes really occur in the brain? Trends Neurosci 1996; 19: 139-143.
27. Whiting P, McKernan RM, Iversen LL. Another mechanism for creating diversity in gamma-aminobutyrate type A receptors: RNA splicing directs expression of two forms of gamma 2 phosphorylation site. Proc Natl Acad Sci USA 1990; 87: 9966-9970.
28. Beneyto M, Abbott A, Hashimoto T, Lewis DA. Lamina-specific alterations in cortical GABA(A) receptor subunit expression in schizophrenia. Cereb Cortex 2011; 21:999-1011.
29. Glausier JR, Lewis DA. Selective pyramidal cell reduction of GABA(A) receptor a1 subunit messenger RNA expression in schizophrenia. Neuropsychopharmacology 2011; 36: 2103-2110.
30. Ohnuma T, Augood SJ, Arai H, McKenna PJ, Emson PC. Measurement of GABAergic parameters in the prefrontal cortex in schizophrenia: focus on GABA content, GABA(A) receptor alpha-1 subunit messenger RNA and human GABA transporter-1 (hGAT-1) messenger RNA expression. Neuroscience 1999; 93: 441-448.
31. Duncan CE, Webster MJ, Rothmond DA, Bahn S, Elashoff M, Weickert CS. Prefrontal GABA(A) receptor alpha-subunit expression in normal postnatal human development and schizophrenia. J Psychiatr Res 2010; 44: 673-681.
32. Fatemi SH, Folsom TD, Rooney RJ, Thuras PD. Expression of GABAA a2-, ß1-and £-receptors are altered significantly in the lateral cerebellum of subjects with schizophrenia, major depression and bipolar disorder. Transl Psychiatry 2013; 3: e303.
33. Wu JQ, Wang X, Beveridge NJ, Tooney PA, Scott RJ, Carr VJ et al. Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia. PLoS One 2012; 7: e36351.
34. Petryshen TL, Middleton FA, Tahl AR, Rockwell GN, Purcell SM, Aldinger KA et al. Genetic investigation of chromosome 5q GABAA receptor subunit genes in schizophrenia. Mol Psychiatry 2005; 10: 1074-1088, 1057.
35. Bullock WM, Cardon K, Bustillo J, Roberts RC, Perrone-Bizzozero NI. Altered expression of genes involved in GABAergic transmission and neuromodulation of granule cell activity in the cerebellum of schizophrenia patients. Am J Psychiatry 2008; 165: 1594-1603.
36. Mueller TM, Haroutunian V, Meador-Woodruff JH. N-Glycosylation of GABAA receptor subunits is altered in Schizophrenia. Neuropsychopharmacology 2014; 39: 528-537.
37. Deng C, Huang X-F. Increased density of GABAA receptors in the superior temporal gyrus in schizophrenia. Exp Brain Res 2006; 168: 587-590.
38. Chen J, Xu Y, Zhang K, Liu Z, Xu C, Shen Y et al. Comparative study of regional homogeneity in schizophrenia and major depressive disorder. Am J Med Genet B Neuropsychiatr Genet 2013; 162B: 36-43.
39. Honea RA, Meyer-Lindenberg A, Hobbs KB, Pezawas L, Mattay VS, Egan MF et al. Is gray matter volume an intermediate phenotype for schizophrenia? A voxel-based morphometry study of patients with schizophrenia and their healthy siblings. Biol Psychiatry 2008; 63: 465-474.
40. Smiley JF. Auditory cortex anatomy and asymmetry in schizophrenia. In: Lajtha, A, Javitt, D, Kantrowitz, J (eds). Handbook of Neurochemistry and Molecular Neurobiology. Springer: Boston, MA USA, 2009, pp 353-381.
41. Helenius A, Aebi M. Roles of N-linked glycans in the endoplasmic reticulum. Annu Rev Biochem. 2004; 73: 1019-1049.
42. Cai G, Salonikidis PS, Fei J, Schwarz W, Schülein R, Reutter W et al. The role of N-glycosylation in the stability, trafficking and GABA-uptake of GABA-transporter 1. Terminal N-glycans facilitate efficient GABA-uptake activity of the GABA transporter. FEBS J 2005; 272: 1625-1638.
43. Dennis JW, Lau KS, Demetriou M, Nabi IR. Adaptive regulation at the cell surface by N-glycosylation. Traffic 2009; 10: 1569-1578.
44. Spiro RG. Protein glycosylation: nature, distribution, enzymatic formation, and disease implications of glycopeptide bonds. Glycobiology 2002; 12: 43R-56R.
45. Roth J, Zuber C, Park S, Jang I, Lee Y, Kysela KG et al. Protein N-glycosylation, protein folding, and protein quality control. Mol Cells 2010; 30: 497-506.
46. Parodi AJ. Protein glucosylation and its role in protein folding. Annu Rev Biochem 2000; 69: 69-93.
47. Ito Y, Takeda Y. Analysis of glycoprotein processing in the endoplasmic reticulum using synthetic oligosaccharides. Proc Jpn Acad Ser B Phys Biol Sci 2012; 88: 31-40.
48. Olivari S, Molinari M. Glycoprotein folding and the role of EDEM1, EDEM2 and EDEM3 in degradation of folding-defective glycoproteins. FEBS Lett 2007; 581: 3658-3664.
49. Tucholski J, Simmons MS, Pinner AL, Haroutunian V, McCullumsmith RE, Meador-Woodruff JH. Abnormal N-linked glycosylation of cortical AMPA receptor subunits in schizophrenia. Schizophr Res 2013; 146: 177-183.
50. Tucholski J, Simmons MS, Pinner AL, McMillan LD, Haroutunian V, Meador-Woodruff JH. N-linked glycosylation of cortical N-methyl-D-aspartate and kainate receptor subunits in schizophrenia. Neuroreport 2013; 24: 688-691.
51. Bauer DE, Haroutunian V, Meador-Woodruff JH, McCullumsmith RE. Abnormal glycosylation of EAAT1 and EAAT2 in prefrontal cortex of elderly patients with schizophrenia. Schizophr Res 2010; 117: 92-98.
52. Sieghart W, Sperk G. Subunit composition, distribution and function of GABA(A) receptor subtypes. Curr Top Med Chem 2002; 2: 795-816.
53. Jacob TC, Moss SJ, Jurd R. GABA(A) receptor trafficking and its role in the dynamic modulation of neuronal inhibition. Nat Rev Neurosci 2008; 9: 331-343.
54. Vithlani M, Terunuma M, Moss SJ. The dynamic modulation of GABA(A) receptor trafficking and its role in regulating the plasticity of inhibitory synapses. Physiol Rev 2011; 91: 1009-1022.
55. Kittler JT, McAinsh K, Moss SJ. Mechanisms of GABAA receptor assembly and trafficking. Mol Neurobiol 2002; 26: 251-268.
56. Essrich C, Lorez M, Benson JA, Fritschy JM, Lüscher B. Postsynaptic clustering of major GABAA receptor subtypes requires the gamma 2 subunit and gephyrin. Nat Neurosci 1998; 1: 563-571.
57. Connolly CN, Krishek BJ, McDonald BJ, Smart TG, Moss SJ. Assembly and cell surface expression of heteromeric and homomeric gamma-aminobutyric acid type A receptors. J Biol Chem 1996; 271: 89-96.
58. Alldred MJ, Mulder-Rosi J, Lingenfelter SE, Chen G, Lüscher B. Distinct gamma2 subunit domains mediate clustering and synaptic function of postsynaptic GABAA receptors and gephyrin. J Neurosci 2005; 25: 594-603.
59. Lewis DA, Cho R, Carter CS. Subunit-selective modulation of GABA type A receptor neurotransmission and cognition in schizophrenia. Am J Psychiatry 2008; 165: 1585-1593.
60. Volk DW. Reciprocal alterations in pre-and postsynaptic inhibitory markers at chandelier cell inputs to pyramidal neurons in schizophrenia. Cereb Cortex 2002; 12: 1063-1070.
61. Buchanan RW, Keefe RSE, Lieberman JA, Barch DM, Csernansky JG, Goff DC et al. A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia. Biol Psychiatry 2011; 69: 442-449.
62. Rubio MD, Wood K, Haroutunian V, Meador-Woodruff JH. Dysfunction of the ubiquitin proteasome and ubiquitin-like systems in schizophrenia. Neuropsycho-pharmacology 2013; 38: 1910-1920.
63. Powchik P, Davidson M, Nemeroff CB, Haroutunian V, Purohit DP, Losonczy M et al. Alzheimer's-disease-related protein in geriatric schizophrenic patients with cognitive impairment. Am J Psychiatry 1993; 150: 1726-1727.
64. Katsel P, Davis KL, Gorman JM, Haroutunian V. Variations in differential gene expression patterns across multiple brain regions in schizophrenia. Schizophr Res 2005; 77: 241-252.
65. Purohit DP, Perl DP, Haroutunian V, Powchik P, Davidson M, Davis KL. Alzheimer disease and related neurodegenerative diseases in elderly patients with schizophrenia: a postmortem neuropathologic study of 100 cases. Arch Gen Psychiatry 1998; 55: 205-211.
66. Hammond JC, Meador-Woodruff JH, Haroutunian V, McCullumsmith RE. AMPA receptor subunit expression in the endoplasmic reticulum in frontal cortex of elderly patients with schizophrenia. PLoS One 2012; 7: e39190.
67. Shan D, Mount D, Moore S, Haroutunian V, Meador-Woodruff JH, McCullumsmith RE. Abnormal partitioning of hexokinase 1 suggests disruption of a glutamate transport protein complex in schizophrenia. Schizophr Res 2014; 154: 1-13.
68. Goebel-Goody SM, Davies KD, Alvestad Linger RM, Freund RK, Browning MD. Phospho-regulation of synaptic and extrasynaptic N-methyl-d-aspartate receptors in adult hippocampal slices. Neuroscience 2009; 158: 1446-1459.
69. Stan AD, Ghose S, Gao XM, Roberts RC, Lewis-Amezcua K, Hatanpaa KJ et al. Human postmortem tissue: what quality markers matter? Brain Res 2006; 1123: 1-11.
70. Bauer DE, Haroutunian V, McCullumsmith RE, Meador-Woodruff JH. Expression of four housekeeping proteins in elderly patients with schizophrenia. J Neural Transm 2009; 116: 487-491.
71. Tretter V, Mukherjee J, Maric H-M, Schindelin H, Sieghart W, Moss SJ. Gephyrin, the enigmatic organizer at GABAergic synapses. Front Cell Neurosci 2012; 6: 23.
72. Jacob TC, Bogdanov YD, Magnus C, Saliba RS, Kittler JT, Haydon PG et al. Gephyrin regulates the cell surface dynamics of synaptic GABAA receptors. J Neurosci 2005; 25: 10469-10478.
73. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc 1995; 57: 289-300.
74. Zhao C, Wang F, Pun FW, Mei L, Ren L, Yu Z et al. Epigenetic regulation on GABRB2 isoforms expression: developmental variations and disruptions in psychotic disorders. Schizophr Res 2012; 134: 260-266.
75. Zhao C, Xu Z, Wang F, Chen J, Ng S-K, Wong P-W et al. Alternative-splicing in the exon-10 region of GABA(A) receptor beta(2) subunit gene: relationships between novel isoforms and psychotic disorders. PLoS One 2009; 4: e6977.
76. McKinley D, Lennon D, Carter D. Cloning, sequence analysis and expression of two forms of mRNA coding for the human β 2 subunit of the GABA A receptor. Mol Brain Res 1995; 28: 175-179.
77. Magrane M, Consortium U. UniProt Knowledgebase: a hub of integrated protein data. Database (Oxford) 2011; 2011: bar009.
78. Sherrington R, Brynjolfsson J, Petursson H, Potter M, Dudleston K, Barraclough B et al. Localization of a susceptibility locus for schizophrenia on chromosome 5. Nature 1988; 336: 164-167.
79. Pato CN, Lander ES, Schulz SC. Prospects for the genetic analysis of schizophrenia. Schizophr Bull 1989; 15: 365-372.
80. Ng S-K, Lo W-S, Pun FW, Zhao C, Yu Z, Chen J et al. A recombination hotspot in a schizophrenia-associated region of GABRB2. PLoS One 2010; 5: e9547.
81. Chen J, Tsang S-Y, Zhao C, Pun FW, Yu Z, Mei L et al. GABRB2 in schizophrenia and bipolar disorder: disease association, gene expression and clinical correlations. Biochem Soc Trans 2009; 37(Pt 6): 1415-1418.
82. Zhao C, Xu Z, Chen J, Yu Z, Tong K-L, Lo W-S et al. Two isoforms of GABA(A) receptor beta2 subunit with different electrophysiological properties: differential expression and genotypical correlations in schizophrenia. Mol Psychiatry 2006; 11: 1092-1105.
83. Pun FW, Zhao C, Lo W-S, Ng S-K, Tsang S-Y, Nimgaonkar V et al. Imprinting in the schizophrenia candidate gene GABRB2 encoding GABA(A) receptor ß(2) subunit. Mol Psychiatry 2011; 16: 557-568.
84. Bayer TA, Falkai P, Maier W. Genetic and non-genetic vulnerability factors in schizophrenia: the basis of the Two hit hypothesis.'. J Psychiatr Res 1999; 33: 543-548.
85. Zhou C, Huang Z, Ding L, Deel ME, Arain FM, Murray CR et al. Altered cortical GABAA receptor composition, physiology, and endocytosis in a mouse model of a human genetic absence epilepsy syndrome. J Biol Chem 2013; 288: 21458-21472.
86. Wu X, Wu Z, Ning G, Guo Y, Ali R, MacDonald RL et al. v-Aminobutyric acid type A (GABAA) receptor a subunits play a direct role in synaptic versus extrasynaptic targeting. J Biol Chem 2012; 287: 27417-27430.
87. Olsen RW, Sieghart W. GABA A receptors: subtypes provide diversity of function and pharmacology. Neuropharmacology 2009; 56: 141-148.
88. Klausberger T, Roberts JDB, Somogyi P. Cell type-and input-specific differences in the number and subtypes of synaptic GABA(A) receptors in the hippocampus. J Neurosci 2002; 22: 2513-2521.
89. Hadingham KL, Wingrove PB, Wafford KA, Bain C, Kemp JA, Palmer KJ et al. Role of the beta subunit in determining the pharmacology of human gamma-aminobutyric acid type A receptors. Mol Pharmacol 1993; 44: 1211-1218.
90. Kang SU, Heo S, Lubec G. Mass spectrometric analysis of GABAA receptor subtypes and phosphorylations from mouse hippocampus. Proteomics 2011; 11: 2171-2181.
91. Laha KT, Tran PN. Multiple tyrosine residues at the GABA binding pocket influence surface expression and mediate kinetics of the GABAA receptor. J Neurochem 2013; 124: 200-209.
92. Uusi-Oukari M, Korpi ER. Regulation of GABA(A) receptor subunit expression by pharmacological agents. Pharmacol Rev 2010; 62: 97-135.
93. Lo WY, Lagrange AH, Hernandez CC, Harrison R, Dell A, Haslam SM et al. Glyco-sylation of β2 subunits regulates GABAA receptor biogenesis and channel gating. J Biol Chem 2010; 285: 31348-31361.
94. Gorrie GH, Vallis Y, Stephenson A, Whitfield J, Browning B, Smart TG et al. Assembly of GABAA receptors composed of alpha1 and beta2 subunits in both cultured neurons and fibroblasts. J Neurosci 1997; 17: 6587-6596.
95. Chen Z-W, Olsen RW. GABAA receptor associated proteins: a key factor regulating GABAA receptor function. J Neurochem 2007; 100: 279-294.