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Molecular Organization and Assembly of the Central Inhibitory Postsynapse

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Cell Communication in Nervous and Immune System

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 43))

Abstract

γ-Amino butyric acid type A (GABAA) receptors are the major sites of fast synaptic inhibition in the brain. GABAA receptors play an important role in regulating neuronal excitability and in addition have been implicated in numerous neurological disorders. In order to understand synaptic inhibition it is important to comprehend the cellular mechanisms, that neurons utilize to regulate the accumulation and regulation of GABAA receptors at postsynaptic inhibitory specializations. Over the past decade a number of GABAA receptor interacting proteins have been identified allowing us to further understand the trafficking, targeting and clustering of these receptors as well as the regulation of receptor stability. In the following review we examine the proteins identified as GABAA receptor binding partners and other components of the inhibitory postsynaptic scaffold, and how they contribute to the construction of inhibitory synapses and the dynamic modulation of synaptic inhibition.

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References

  1. Angelotti TP, Macdonald RL (1993) Assembly of GABAA receptor subunits: alpha 1 beta 1 and alpha 1 beta 1 gamma 2S subunits produce unique ion channels with dissimilar single-channel properties. J Neurosci 13:1429–1440

    PubMed  CAS  Google Scholar 

  2. Beck M, Brickley K, Wilkinson HL, Sharma S, Smith M, Chazot PL, Pollard S, Stephenson FA (2002) Identification, molecular cloning, and characterization of a novel GABAA receptor-associated protein, GRIF-1. J Biol Chem 277:30079–30090

    PubMed  CAS  Google Scholar 

  3. Bedford FK, Kittler JT, Muller E, Thomas P, Uren JM, Merlo D, Wisden W, Triller A, Smart TG, Moss SJ (2001) GABA(A) receptor cell surface number and subunit stability are regulated by the ubiquitin-like protein Plic-1. Nat Neurosci 4:908–916

    PubMed  CAS  Google Scholar 

  4. Blum BP, Mann JJ (2002) The GABAergic system in schizophrenia. Int J Neuropsychopharmacol 5:159–179

    PubMed  CAS  Google Scholar 

  5. Bohme I, Rabe H, Luddens H (2004) Four amino acids in the alpha subunits determine the gamma-aminobutyric acid sensitivities of GABAA receptor subtypes. J Biol Chem 279:35193–35200

    PubMed  Google Scholar 

  6. Brandon N, Jovanovic J, Moss S (2002) Multiple roles of protein kinases in the modulation of gamma-aminobutyric acid(A) receptor function and cell surface expression. Pharmacol Ther 94:113–122

    PubMed  CAS  Google Scholar 

  7. Brickley SG, Cull-Candy SG, Farrant M (1996) Development of a tonic form of synaptic inhibition in rat cerebellar granule cells resulting from persistent activation of GABAA receptors. J Physiol 497 (Pt 3):753–759

    Google Scholar 

  8. Brickley SG, Cull-Candy SG, Farrant M (1999) Single-channel properties of synaptic and extrasynaptic GABAA receptors suggest differential targeting of receptor subtypes. J Neurosci 19:2960–2973

    PubMed  CAS  Google Scholar 

  9. Brickley SG, Revilla V, Cull-Candy SG, Wisden W, Farrant M (2001) Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance. Nature 409:88–92

    PubMed  CAS  Google Scholar 

  10. Brown N, Kerby J, Bonnert TP, Whiting PJ, Wafford KA (2002) Pharmacological characterization of a novel cell line expressing human alpha(4)beta(3)delta GABA(A) receptors. Br J Pharmacol 136:965–974

    PubMed  CAS  Google Scholar 

  11. Brunig I, Scotti E, Sidler C, Fritschy JM (2002) Intact sorting, targeting, and clustering of gamma-aminobutyric acid A receptor subtypes in hippocampal neurons in vitro. J Comp Neurol 443:43–55

    PubMed  CAS  Google Scholar 

  12. Burette A, Wyszynski M, Valtschanoff JG, Sheng M, Weinberg RJ (1999) Characterization of glutamate receptor interacting protein-immunopositive neurons in cerebellum and cerebral cortex of the albino rat. J Comp Neurol 411:601–612

    PubMed  CAS  Google Scholar 

  13. Chang Y, Wang R, Barot S, Weiss DS (1996) Stoichiometry of a recombinant GABAA receptor. J Neurosci 16:5415–5424

    PubMed  CAS  Google Scholar 

  14. Charych EI, Yu W, Miralles CP, Serwanski DR, Li X, Rubio M, De Blas AL (2004a) The brefeldin A-inhibited GDP/GTP exchange factor 2, a protein involved in vesicular trafficking, interacts with the beta subunits of the GABA receptors. J Neurochem 90:173–189

    PubMed  CAS  Google Scholar 

  15. Charych EI, Yu W, Li R, Serwanski DR, Miralles CP, Li X, Yang BY, Pinal N, Walikonis R, De Blas AL (2004b) A four PDZ domain-containing splice variant form of GRIP1 is localized in GABAergic and glutamatergic synapses in the brain. J Biol Chem 279:38978–38990

    PubMed  CAS  Google Scholar 

  16. Chen ZW, Chang CS, Leil TA, Olcese R, Olsen RW (2005) GABAA Receptor-associated protein regulates GABAA receptor cell-surface number in Xenopus laevis oocytes. Mol Pharmacol 68:152–159

    PubMed  CAS  Google Scholar 

  17. Chih B, Engelman H, Scheiffele P (2005) Control of excitatory and inhibitory synapse formation by neuroligins. Science 307:1324–1328

    PubMed  CAS  Google Scholar 

  18. Choquet D, Triller A (2003) The role of receptor diffusion in the organization of the postsynaptic membrane. Nat Rev Neurosci 4:251–265

    PubMed  CAS  Google Scholar 

  19. Cinar H, Barnes EM Jr (2001) Clathrin-independent endocytosis of GABA(A) receptors in HEK 293 cells. Biochemistry 40:14030–14036

    PubMed  CAS  Google Scholar 

  20. Connolly CN, Uren JM, Thomas P, Gorrie GH, Gibson A, Smart TG, Moss SJ (1999) Subcellular localization and endocytosis of homomeric gamma2 subunit splice variants of gamma-aminobutyric acid type A receptors. Mol Cell Neurosci 13:259–271

    PubMed  CAS  Google Scholar 

  21. Cossart R, Bernard C, Ben-Ari Y (2005) Multiple facets of GABAergic neurons and synapses: multiple fates of GABA signalling in epilepsies. Trends Neurosci 28:108–115

    PubMed  CAS  Google Scholar 

  22. Coulter DA (2001) Epilepsy-associated plasticity in gamma-aminobutyric acid receptor expression, function, and inhibitory synaptic properties. Int Rev Neurobiol 45:237–252

    Article  PubMed  CAS  Google Scholar 

  23. Craig AM, Banker G, Chang W, McGrath ME, Serpinskaya AS (1996) Clustering of gephyrin at GABAergic but not glutamatergic synapses in cultured rat hippocampal neurons. J Neurosci 16:3166–3177

    PubMed  CAS  Google Scholar 

  24. Dahan M, Levi S, Luccardini C, Rostaing P, Riveau B, Triller A (2003) Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking. Science 302:442–445

    PubMed  CAS  Google Scholar 

  25. Danglot L, Triller A, Bessis A (2003) Association of gephyrin with synaptic and extrasynaptic GABAA receptors varies during development in cultured hippocampal neurons. Mol Cell Neurosci 23:264–278

    PubMed  CAS  Google Scholar 

  26. Davies PA, Hanna MC, Hales TG, Kirkness EF (1997) Insensitivity to anaesthetic agents conferred by a class of GABA(A) receptor subunit. Nature 385:820–823

    PubMed  CAS  Google Scholar 

  27. Dean C, Scholl FG, Choih J, DeMaria S, Berger J, Isacoff E, Scheiffele P (2003) Neurexin mediates the assembly of presynaptic terminals. Nat Neurosci 6:708–716

    PubMed  CAS  Google Scholar 

  28. DeLorey TM, Handforth A, Anagnostaras SG, Homanics GE, Minassian BA, Asatourian A, Fanselow MS, Delgado-Escueta A, Ellison GD, Olsen RW (1998) Mice lacking the beta3 subunit of the GABAA receptor have the epilepsy phenotype and many of the behavioral characteristics of Angelman syndrome. J Neurosci 18:8505–8514

    PubMed  CAS  Google Scholar 

  29. DeSouza S, Fu J, States BA, Ziff EB (2002) Differential palmitoylation directs the AMPA receptor-binding protein ABP to spines or to intracellular clusters. J Neurosci 22:3493–3503

    PubMed  CAS  Google Scholar 

  30. Dong H, Zhang P, Liao D, Huganir RL (1999) Characterization, expression, and distribution of GRIP protein. Ann NY Acad Sci 868:535–540

    PubMed  CAS  Google Scholar 

  31. Dong H, O'Brien RJ, Fung ET, Lanahan AA, Worley PF, Huganir RL (1997) GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors. Nature 386:279–284

    PubMed  CAS  Google Scholar 

  32. Dumoulin A, Levi S, Riveau B, Gasnier B, Triller A (2000) Formation of mixed glycine and GABAergic synapses in cultured spinal cord neurons. Eur J Neurosci 12:3883–3892

    PubMed  CAS  Google Scholar 

  33. Ebert V, Scholze P, Fuchs K, Sieghart W (1999) Identification of subunits mediating clustering of GABA(A) receptors by rapsyn. Neurochem Int 34:453–463

    PubMed  CAS  Google Scholar 

  34. El-Husseini Ael D, Schnell E, Dakoji S, Sweeney N, Zhou Q, Prange O, Gauthier-Campbell C, Aguilera-Moreno A, Nicoll RA, Bredt DS (2002) Synaptic strength regulated by palmitate cycling on PSD-95. Cell 108:849–863

    Google Scholar 

  35. Essrich C, Lorez M, Benson JA, Fritschy JM, Luscher B (1998) Postsynaptic clustering of major GABAA receptor subtypes requires the gamma 2 subunit and gephyrin. Nat Neurosci 1:563–571

    PubMed  CAS  Google Scholar 

  36. Farrant M, Nusser Z (2005) Variations on an inhibitory theme: phasic and tonic activation of GABA(A) receptors. Nat Rev Neurosci 6:215–229

    PubMed  CAS  Google Scholar 

  37. Farrar SJ, Whiting PJ, Bonnert TP, McKernan RM (1999) Stoichiometry of a ligand-gated ion channel determined by fluorescence energy transfer. J Biol Chem 274:10100–10104

    PubMed  CAS  Google Scholar 

  38. Feng G, Tintrup H, Kirsch J, Nichol MC, Kuhse J, Betz H, Sanes JR (1998) Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity. Science 282:1321–1324

    PubMed  CAS  Google Scholar 

  39. Fisher JL, Macdonald RL (1997) Single channel properties of recombinant GABAA receptors containing gamma 2 or delta subtypes expressed with alpha 1 and beta 3 subtypes in mouse L929 cells. J Physiol 505(Pt 2):283–297

    PubMed  CAS  Google Scholar 

  40. Fu Z, Washbourne P, Ortinski P, Vicini S (2003) Functional excitatory synapses in HEK293 cells expressing neuroligin and glutamate receptors. J Neurophysiol 90:3950–3957

    PubMed  CAS  Google Scholar 

  41. Graf ER, Zhang X, Jin SX, Linhoff MW, Craig AM (2004) Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Cell 119:1013–1026

    PubMed  CAS  Google Scholar 

  42. Haas KF, Macdonald RL (1999) GABAA receptor subunit gamma2 and delta subtypes confer unique kinetic properties on recombinant GABAA receptor currents in mouse fibroblasts. J Physiol 514(Pt 1):27–45

    PubMed  CAS  Google Scholar 

  43. Herring D, Huang R, Singh M, Robinson LC, Dillon GH, Leidenheimer NJ (2003) Constitutive GABAA receptor endocytosis is dynamin-mediated and dependent on a dileucine AP2 adaptin-binding motif within the beta 2 subunit of the receptor. J Biol Chem 278:24046–24052

    PubMed  CAS  Google Scholar 

  44. Heuser JE, Anderson RG (1989) Hypertonic media inhibit receptor-mediated endocytosis by blocking clathrin-coated pit formation. J Cell Biol 108:389–400

    PubMed  CAS  Google Scholar 

  45. Ichtchenko K, Nguyen T, Sudhof TC (1996) Structures, alternative splicing, and neurexin binding of multiple neuroligins. J Biol Chem 271:2676–2682

    PubMed  CAS  Google Scholar 

  46. Jacobs TC, Bogdanov YD, Magnus C, Saliba RS, Kittler JT, Haydon PG, Moss SJ (2005) Gephyrin regulates the cell surface dynamics of synaptic GABAA receptors. J Neurosci 25:10469–10478

    Google Scholar 

  47. Kanematsu T, Jang IS, Yamaguchi T, Nagahama H, Yoshimura K, Hidaka K, Matsuda M, Takeuchi H, Misumi Y, Nakayama K, Yamamoto T, Akaike N, Hirata M, Nakayama K (2002) Role of the PLC-related, catalytically inactive protein p130 in GABA(A) receptor function. Embo J 21:1004–1011

    PubMed  CAS  Google Scholar 

  48. Keller CA, Yuan X, Panzanelli P, Martin ML, Alldred M, Sassoe-Pognetto M, Luscher B (2004) The gamma2 subunit of GABA(A) receptors is a substrate for palmitoylation by GODZ. J Neurosci 24:5881–5891

    PubMed  CAS  Google Scholar 

  49. Kirsch J, Wolters I, Triller A, Betz H (1993) Gephyrin antisense oligonucleotides prevent glycine receptor clustering in spinal neurons. Nature 366:745–748

    PubMed  CAS  Google Scholar 

  50. Kittler JT, Moss SJ (2003) Modulation of GABAA receptor activity by phosphorylation and receptor trafficking: implications for the efficacy of synaptic inhibition. Curr Opin Neurobiol 13:341–347

    PubMed  CAS  Google Scholar 

  51. Kittler JT, Arancibia-Carcamo IL, Moss SJ (2004a) Association of GRIP1 with a GABA(A) receptor associated protein suggests a role for GRIP1 at inhibitory synapses. Biochem Pharmacol 68:1649–1654

    PubMed  CAS  Google Scholar 

  52. Kittler JT, Delmas P, Jovanovic JN, Brown DA, Smart TG, Moss SJ (2000) Constitutive endocytosis of GABAA receptors by an association with the adaptin AP2 complex modulates inhibitory synaptic currents in hippocampal neurons. J Neurosci 20:7972–7977

    PubMed  CAS  Google Scholar 

  53. Kittler JT, Rostaing P, Schiavo G, Fritschy JM, Olsen R, Triller A, Moss SJ (2001) The subcellular distribution of GABARAP and its ability to interact with NSF suggest a role for this protein in the intracellular transport of GABA(A) receptors. Mol Cell Neurosci 18:13–25

    PubMed  CAS  Google Scholar 

  54. Kittler JT, Thomas P, Tretter V, Bogdanov YD, Haucke V, Smart TG, Moss SJ (2004b) Huntingtin-associated protein 1 regulates inhibitory synaptic transmission by modulating gamma-aminobutyric acid type A receptor membrane trafficking. Proc Natl Acad Sci USA 101:12736–12741

    PubMed  CAS  Google Scholar 

  55. Kittler JT, Chen G, Honing S, Bogdanov YD, McAinsh K, Arancibia-Carcamo IL, Jovanovic JN, Pangalos MN, Haucke V, Yan Z, Moss SJ (2005) Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission. Proc Natl Acad Sci USA 102:14871–6

    PubMed  CAS  Google Scholar 

  56. Kleijnen MF, Shih AH, Zhou P, Kumar S, Soccio RE, Kedersha NL, Gill G, Howley PM (2000) The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome. Mol Cell 6:409–419

    PubMed  CAS  Google Scholar 

  57. Kneussel M, Hermann A, Kirsch J, Betz H (1999a) Hydrophobic interactions mediate binding of the glycine receptor beta-subunit to gephyrin. J Neurochem 72:1323–1326

    PubMed  CAS  Google Scholar 

  58. Kneussel M, Brandstatter JH, Laube B, Stahl S, Muller U, Betz H (1999b) Loss of postsynaptic GABA(A) receptor clustering in gephyrin-deficient mice. J Neurosci 19:9289–9297

    PubMed  CAS  Google Scholar 

  59. Knight AR, Stephenson FA, Tallman JF, Ramabahdran TV (2000) Monospecific antibodies as probes for the stoichiometry of recombinant GABA(A) receptors. Receptors Channels 7:213–226

    PubMed  CAS  Google Scholar 

  60. Knuesel I, Mastrocola M, Zuellig RA, Bornhauser B, Schaub MC, Fritschy JM (1999) Short communication: altered synaptic clustering of GABAA receptors in mice lacking dystrophin (mdx mice). Eur J Neurosci 11:4457–4462

    PubMed  CAS  Google Scholar 

  61. Krishek BJ, Moss SJ, Smart TG (1996) Homomeric beta 1 gamma-aminobutyric acid A receptor-ion channels: evaluation of pharmacological and physiological properties. Mol Pharmacol 49:494–504

    PubMed  CAS  Google Scholar 

  62. Kunig G, Leenders KL, Sanchez-Pernaute R, Antonini A, Vontobel P, Verhagen A, Gunther I (2000) Benzodiazepine receptor binding in Huntington's disease: [11C]flumazenil uptake measured using positron emission tomography. Ann Neurol 47:644–648

    PubMed  CAS  Google Scholar 

  63. Laurie DJ, Wisden W, Seeburg PH (1992a) The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development. J Neurosci 12:4151–4172

    PubMed  CAS  Google Scholar 

  64. Laurie DJ, Seeburg PH, Wisden W (1992b) The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. II. Olfactory bulb and cerebellum. J Neurosci 12:1063–1076

    PubMed  CAS  Google Scholar 

  65. Lavoie AM, Tingey JJ, Harrison NL, Pritchett DB, Twyman RE (1997) Activation and deactivation rates of recombinant GABA(A) receptor channels are dependent on alpha-subunit isoform. Biophys J 73:2518–2526

    Article  PubMed  CAS  Google Scholar 

  66. Leil TA, Chen ZW, Chang CS, Olsen RW (2004) GABAA receptor-associated protein traffics GABAA receptors to the plasma membrane in neurons. J Neurosci 24:11429–11438

    PubMed  CAS  Google Scholar 

  67. Levi S, Logan SM, Tovar KR, Craig AM (2004) Gephyrin is critical for glycine receptor clustering but not for the formation of functional GABAergic synapses in hippocampal neurons. J Neurosci 24:207–217

    PubMed  CAS  Google Scholar 

  68. Levi S, Grady RM, Henry MD, Campbell KP, Sanes JR, Craig AM (2002) Dystroglycan is selectively associated with inhibitory GABAergic synapses but is dispensable for their differentiation. J Neurosci 22:4274–4285

    PubMed  CAS  Google Scholar 

  69. Levinson JN, El-Husseini A (2005) New players tip the scales in the balance between excitatory and inhibitory synapses. Mol Pain 1:12

    PubMed  Google Scholar 

  70. Levinson JN, Chery N, Huang K, Wong TP, Gerrow K, Kang R, Prange O, Wang YT, El-Husseini A (2005) Neuroligins mediate excitatory and inhibitory synapse formation: involvement of PSD-95 and neurexin-1beta in neuroligin-induced synaptic specificity. J Biol Chem 280:17312–17319

    PubMed  CAS  Google Scholar 

  71. Lewis DA (2000) GABAergic local circuit neurons and prefrontal cortical dysfunction in schizophrenia. Brain Res Brain Res Rev 31:270–276

    PubMed  CAS  Google Scholar 

  72. Li RW, Serwanski DR, Miralles CP, Li X, Charych E, Riquelme R, Huganir RL, de Blas AL (2005) GRIP1 in GABAergic synapses. J Comp Neurol 488:11–27

    PubMed  CAS  Google Scholar 

  73. Malizia AL (1999) What do brain imaging studies tell us about anxiety disorders? J Psychopharmacol 13:372–378

    Article  PubMed  CAS  Google Scholar 

  74. Meyer G, Kirsch J, Betz H, Langosch D (1995) Identification of a gephyrin binding motif on the glycine receptor beta subunit. Neuron 15:563–572

    PubMed  CAS  Google Scholar 

  75. Mody I, Pearce RA (2004) Diversity of inhibitory neurotransmission through GABA(A) receptors. Trends Neurosci 27:569–575

    PubMed  CAS  Google Scholar 

  76. Mohler H, Crestani F, Rudolph U (2001) GABA(A)-receptor subtypes: a new pharmacology. Curr Opin Pharmacol 1:22–25

    PubMed  CAS  Google Scholar 

  77. Morrow AL, VanDoren MJ, Penland SN, Matthews DB (2001) The role of GABAergic neuroactive steroids in ethanol action, tolerance and dependence. Brain Res Brain Res Rev 37:98–109

    PubMed  CAS  Google Scholar 

  78. Moss SJ, Smart TG (2001) Constructing inhibitory synapses. Nat Rev Neurosci 2:240–250

    PubMed  CAS  Google Scholar 

  79. Neelands TR, Macdonald RL (1999) Incorporation of the pi subunit into functional gamma-aminobutyric Acid(A) receptors. Mol Pharmacol 56:598–610

    PubMed  CAS  Google Scholar 

  80. Nusser Z, Cull-Candy S, Farrant M (1997) Differences in synaptic GABA(A) receptor number underlie variation in GABA mini amplitude. Neuron 19:697–709

    PubMed  CAS  Google Scholar 

  81. Nusser Z, Sieghart W, Somogyi P (1998a) Segregation of different GABAA receptors to synaptic and extrasynaptic membranes of cerebellar granule cells. J Neurosci 18:1693–1703

    PubMed  CAS  Google Scholar 

  82. Nusser Z, Hajos N, Somogyi P, Mody I (1998b) Increased number of synaptic GABA(A) receptors underlies potentiation at hippocampal inhibitory synapses. Nature 395:172–177

    PubMed  CAS  Google Scholar 

  83. Nusser Z, Sieghart W, Benke D, Fritschy JM, Somogyi P (1996) Differential synaptic localization of two major gamma-aminobutyric acid type A receptor alpha subunits on hippocampal pyramidal cells. Proc Natl Acad Sci USA 93:11939–11944

    PubMed  CAS  Google Scholar 

  84. Nutt DJ, Malizia AL (2001) New insights into the role of the GABA(A)-benzodiazepine receptor in psychiatric disorder. Br J Psychiatry 179:390–396

    PubMed  CAS  Google Scholar 

  85. Olsen RW, DeLorey TM, Gordey M, Kang MH (1999) GABA receptor function and epilepsy. Adv Neurol 79:499–510

    PubMed  CAS  Google Scholar 

  86. Pfeiffer F, Graham D, Betz H (1982) Purification by affinity chromatography of the glycine receptor of rat spinal cord. J Biol Chem 257:9389–9393

    PubMed  CAS  Google Scholar 

  87. Pirker S, Schwarzer C, Wieselthaler A, Sieghart W, Sperk G (2000) GABA(A) receptors: immunocytochemical distribution of 13 subunits in the adult rat brain. Neuroscience 101:815–850

    PubMed  CAS  Google Scholar 

  88. Prange O, Wong TP, Gerrow K, Wang YT, El-Husseini A (2004) A balance between excitatory and inhibitory synapses is controlled by PSD-95 and neuroligin. Proc Natl Acad Sci USA 101:13915–13920

    PubMed  CAS  Google Scholar 

  89. Ramming M, Kins S, Werner N, Hermann A, Betz H, Kirsch J (2000) Diversity and phylogeny of gephyrin: tissue-specific splice variants, gene structure, and sequence similarities to molybdenum cofactor-synthesizing and cytoskeleton-associated proteins. Proc Natl Acad Sci USA 97:10266–10271

    PubMed  CAS  Google Scholar 

  90. Rathenberg J, Kittler JT, Moss SJ (2004) Palmitoylation regulates the clustering and cell surface stability of GABAA receptors. Mol Cell Neurosci 26:251–257

    PubMed  CAS  Google Scholar 

  91. Rudolph U, Crestani F, Mohler H (2001) GABA(A) receptor subtypes: dissecting their pharmacological functions. Trends Pharmacol Sci 22:188–194

    PubMed  CAS  Google Scholar 

  92. Schaerer MT, Kannenberg K, Hunziker P, Baumann SW, Sigel E (2001) Interaction between GABA(A) receptor beta subunits and the multifunctional protein gC1q-R. J Biol Chem 276:26597–26604

    PubMed  CAS  Google Scholar 

  93. Scheiffele P, Fan J, Choih J, Fetter R, Serafini T (2000) Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell 101:657–669

    PubMed  CAS  Google Scholar 

  94. Schofield PR, Darlison MG, Fujita N, Burt DR, Stephenson FA, Rodriguez H, Rhee LM, Ramachandran J, Reale V, Glencorse TA et al. (1987) Sequence and functional expression of the GABA A receptor shows a ligand-gated receptor super-family. Nature 328:221–227

    PubMed  CAS  Google Scholar 

  95. Schwartz-Bloom RD, Sah R (2001) gamma-Aminobutyric acid(A) neurotransmission and cerebral ischemia. J Neurochem 77:353–371

    PubMed  CAS  Google Scholar 

  96. Schwarz G, Schrader N, Mendel RR, Hecht HJ, Schindelin H (2001) Crystal structures of human gephyrin and plant Cnx1 G domains: comparative analysis and functional implications. J Mol Biol 312:405–418

    PubMed  CAS  Google Scholar 

  97. Shivers BD, Killisch I, Sprengel R, Sontheimer H, Kohler M, Schofield PR, Seeburg PH (1989) Two novel GABAA receptor subunits exist in distinct neuronal subpopulations. Neuron 3:327–337

    PubMed  CAS  Google Scholar 

  98. Sieghart W, Fuchs K, Tretter V, Ebert V, Jechlinger M, Hoger H, Adamiker D (1999) Structure and subunit composition of GABA(A) receptors. Neurochem Int 34:379–385

    PubMed  CAS  Google Scholar 

  99. Smotrys JE, Linder ME (2004) Palmitoylation of intracellular signaling proteins: regulation and function. Annu Rev Biochem 73:559–587

    PubMed  CAS  Google Scholar 

  100. Song JY, Ichtchenko K, Sudhof TC, Brose N (1999) Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses. Proc Natl Acad Sci USA 96:1100–1105

    PubMed  CAS  Google Scholar 

  101. Song R, Segal G, Messing J (2004) Expression of the sorghum 10-member kafirin gene cluster in maize endosperm. Nucleic Acids Res 32:e189

    Google Scholar 

  102. Stell BM, Brickley SG, Tang CY, Farrant M, Mody I (2003) Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by delta subunit-containing GABAA receptors. Proc Natl Acad Sci USA 100:14439–14444

    PubMed  CAS  Google Scholar 

  103. Tardin C, Cognet L, Bats C, Lounis B, Choquet D (2003) Direct imaging of lateral movements of AMPA receptors inside synapses. Embo J 22:4656–4665

    PubMed  CAS  Google Scholar 

  104. Terunuma M, Jang IS, Ha SH, Kittler JT, Kanematsu T, Jovanovic JN, Nakayama KI, Akaike N, Ryu SH, Moss SJ, Hirata M (2004) GABAA receptor phospho-dependent modulation is regulated by phospholipase C-related inactive protein type 1, a novel protein phosphatase 1 anchoring protein. J Neurosci 24:7074–7084

    PubMed  CAS  Google Scholar 

  105. Thomas P, Mortensen M, Hosie AM, Smart TG (2005) Dynamic mobility of functional GABAA receptors at inhibitory synapses. Nat Neurosci 8:889

    PubMed  CAS  Google Scholar 

  106. Tretter V, Ehya N, Fuchs K, Sieghart W (1997) Stoichiometry and assembly of a recombinant GABAA receptor subtype. J Neurosci 17:2728–2737

    PubMed  CAS  Google Scholar 

  107. Unwin N (1993) Nicotinic acetylcholine receptor at 9 A resolution. J Mol Biol 229:1101–1124

    PubMed  CAS  Google Scholar 

  108. van Rijnsoever C, Sidler C, Fritschy JM (2005) Internalized GABA-receptor subunits are transferred to an intracellular pool associated with the postsynaptic density. Eur J Neurosci 21:327–338

    PubMed  Google Scholar 

  109. Varoqueaux F, Jamain S, Brose N (2004) Neuroligin 2 is exclusively localized to inhibitory synapses. Eur J Cell Biol 83:449–456

    PubMed  CAS  Google Scholar 

  110. Wang H, Olsen RW (2000) Binding of the GABA(A) receptor-associated protein (GABARAP) to microtubules and microfilaments suggests involvement of the cytoskeleton in GABARAP–GABA(A) receptor interaction. J Neurochem 75:644–655

    PubMed  CAS  Google Scholar 

  111. Wang H, Bedford FK, Brandon NJ, Moss SJ, Olsen RW (1999) GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton. Nature 397:69–72

    PubMed  CAS  Google Scholar 

  112. Washbourne P, Dityatev A, Scheiffele P, Biederer T, Weiner JA, Christopherson KS, El-Husseini A (2004) Cell adhesion molecules in synapse formation. J Neurosci 24:9244–9249

    PubMed  CAS  Google Scholar 

  113. Wisden W, Laurie DJ, Monyer H, Seeburg PH (1992) The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon. J Neurosci 12:1040–1062

    PubMed  CAS  Google Scholar 

  114. Wooltorton JR, Moss SJ, Smart TG (1997) Pharmacological and physiological characterization of murine homomeric beta3 GABA(A) receptors. Eur J Neurosci 9:2225–2235

    PubMed  CAS  Google Scholar 

  115. Wu AL, Wang J, Zheleznyak A, Brown EJ (1999) Ubiquitin-related proteins regulate interaction of vimentin intermediate filaments with the plasma membrane. Mol Cell 4:619–625

    PubMed  CAS  Google Scholar 

  116. Wyszynski M, Valtschanoff JG, Naisbitt S, Dunah AW, Kim E, Standaert DG, Weinberg R, Sheng M (1999) Association of AMPA receptors with a subset of glutamate receptor-interacting protein in vivo. J Neurosci 19:6528–6537

    PubMed  CAS  Google Scholar 

  117. Yoshimura K, Takeuchi H, Sato O, Hidaka K, Doira N, Terunuma M, Harada K, Ogawa Y, Ito Y, Kanematsu T, Hirata M (2001) Interaction of p130 with, and consequent inhibition of, the catalytic subunit of protein phosphatase 1alpha. J Biol Chem 276:17908–17913

    PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Dr. J.T. Kittler for critical reading of this manuscript. ILAC is the recipient of a Wellcome trust prize Studentship and SJM is supported by Grants from the MRC (UK), the Wellcome trust and NIH NINDS grants NS047478, NS048045 & NS051195.

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Authors and Affiliations

  1. Department of Pharmacology, University College London, Gower Street, WC1E 6BT, London, UK

    I. Lorena Arancibia-Carcamo

  2. Department of Neuroscience, School of Medicine, University of Pennsylvania, 215 Stemmler Hall, 19104/6074, Philadelphia, PA, USA

    Stephen J. Moss

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  1. I. Lorena Arancibia-Carcamo
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  2. Stephen J. Moss
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Correspondence to Stephen J. Moss .

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Eckart D. Gundelfinger Constanze I. Seidenbecher Burkhart Schraven

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© 2006 Springer-Verlag Berlin Heidelberg

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Arancibia-Carcamo, I.L., Moss, S.J. (2006). Molecular Organization and Assembly of the Central Inhibitory Postsynapse. In: Gundelfinger, E.D., Seidenbecher, C.I., Schraven, B. (eds) Cell Communication in Nervous and Immune System. Results and Problems in Cell Differentiation, vol 43. Springer, Berlin, Heidelberg . https://doi.org/10.1007/400_017

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