Molecular Organization and Regulation of Glutamate Receptors in Developing and Adult Mammalian Central Nervous Systems

  • E. Molnár


The amino acid glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS), and it exerts its physiological effects by binding to a number of different ionotropic (ligand-gated ion channels) and metabotropic (G-protein-coupled) glutamate receptors. In addition to excitatory neurotransmission, glutamate receptors play an essential role in neuronal differentiation, plastic changes in efficacy of synaptic transmission, neurodegeneration, and neuronal cell death. The application of molecular cloning technology identified a complex and diverse receptor family. To date, 18 different ionotropic glutamate receptor (iGluR) genes and 8 genes for metabotropic glutamate receptors (mGluRs) have been identified from mammals. The availability of more selective drugs, gene knockout mice and high-resolution immunohistochemical studies started to reveal the pharmacological and functional properties of individual iGluR subunits and mGluR isoforms. Wide range of studies in recent years indicated that the activity and synaptic distribution of various glutamate receptors are dynamically regulated by phosphorylation and protein–protein interactions, which are key mechanisms in mediating synaptic plasticity. This chapter reviews some of the recent progress in glutamate receptor research with special emphasis on the molecular diversity of this receptor system and its implications for neuronal development and synaptic plasticity.


Glutamate Receptor Synaptic Plasticity Glutamatergic Synapse Postnatal Development NR2B Subunit 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of Abbreviations:


AMPAR-binding protein


α-amino-3-hydroxy-5-methyl-4-isoxazole propionate


Ca2+/calmodulin-dependent protein kinase II


central nervous system


γ-aminobutyric acid


glutamate receptor interacting protein 1


ionotropic glutamate receptor


inositol 1,4,5-trisphosphate


long-term depression


long-term potentiation


metabotropic glutamate receptor


myosin light-chain kinase




N-ethylmaleimide-sensitive factor


phosphatidylinositol 3-kinase


protein interacting with C-kinase 1


protein kinase A


protein kinase C


phospholipase C


postsynaptic density


reverse transcriptase polymerase chain reaction


synapse-associated protein



The author is grateful to the Medical Research Council and the Wellcome Trust for financial support.


  1. Airas JM, Betz H, Far E. 2001. PKC phosphorylation of a conserved serine residue in the C-terminus of group III metabotropic glutamate receptors inhibits calmodulin binding. FEBS Lett 494: 60–63.PubMedCrossRefGoogle Scholar
  2. Ali DW, Salter MW. 2001. NMDA receptor regulation by Src kinase signalling in excitatory synaptic transmission and plasticity. Curr Opin Neurobiol 11: 336–342.PubMedCrossRefGoogle Scholar
  3. Ango F, Prezeau L, Muller T, Tu JC, Xiao B, et al. 2001. Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer. Nature 411: 962–965.PubMedCrossRefGoogle Scholar
  4. Ashby MC, De La Rue Sa, Ralph GS, Uney J, Collingridge GL, et al. 2004. Removal of AMPA receptors (AMPARs) from synapses is preceded by transient endocytosis of extrasynaptic AMPARs. J Neurosci 24: 5172–5176.PubMedCrossRefGoogle Scholar
  5. Azkue JJ, Mateos JM, Elezgarai I, Benitez R, Osorio A, et al. 2000. The metabotropic glutamate receptor subtype mGluR2/3 is located at extrasynaptic loci in rat spinal dorsal horn synapses. Neurosci Lett 287: 236–238.PubMedCrossRefGoogle Scholar
  6. Bahn S, Volk B, Wisden W. 1994. Kainate receptor gene expression in the developing rat brain. J Neurosci 14: 5525–5547.PubMedGoogle Scholar
  7. Banke TG, Bowie D, Lee H, Huganir RL, Schousboe A, et al. 2000. Control of GluR1 AMPA receptor function by cAMP-dependent protein kinase. J Neurosci 20: 89–102.PubMedGoogle Scholar
  8. Barria A, Malinow R. 2002. Subunit-specific NMDA receptor trafficking to synapses. Neuron 35: 345–353.PubMedCrossRefGoogle Scholar
  9. Barria A, Malinow R. 2005. NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII. Neuron 48: 289–301.PubMedCrossRefGoogle Scholar
  10. Baude A, Nusser Z, Molnár E, McIlhinney RAJ, Somogyi P. 1995. High-resolution immunogold localization of AMPA type glutamate receptor subunits at synaptic and non-synaptic sites in rat hippocampus. Neuroscience 69: 1031–1055.PubMedCrossRefGoogle Scholar
  11. Baude A, Nusser Z, Roberts JD, Mulvihill E, McIlhinney RAJ, et al. 1993. The metabotropic glutamate receptor (mGluR1 alpha) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron 11: 771–787.PubMedCrossRefGoogle Scholar
  12. Bear MF, Abraham WC. 1996. Long-term depression in hippocampus. Annu Rev Neurosci 19: 437–462.PubMedCrossRefGoogle Scholar
  13. Beattie EC, Carroll RC, Yu X, Morishita W, Yasuda H, et al. 2000. Regulation of AMPA receptor endocytosis by a signalling mechanism shared with LTD. Nat Neurosci 3: 1291–1300.PubMedCrossRefGoogle Scholar
  14. Bernard A, Ferhat L, Dessi F, Charton G, Represa A, et al. 1999. Q/R editing of the rat GluR5 and GluR6 kainate receptors in vivo and in vitro: Evidence for independent developmental, pathological and cellular regulation. Eur J Neurosci 11: 604–616.PubMedCrossRefGoogle Scholar
  15. Bliss TV, Collingridge GL. 1993. Asynaptic model of memory: Long-term potentiation in the hippocampus. Nature 361: 31–39.PubMedCrossRefGoogle Scholar
  16. Bradley SR, Rees HD, Yi H, Levey AI, Conn PJ. 1998. Distribution and developmental regulation of metabotropic glutamate receptor 7a in rat brain. J Neurochem 71: 636–645.PubMedCrossRefGoogle Scholar
  17. Bredt DS, Nicoll RA. 2003. AMPA receptor trafficking at excitatory synapses. Neuron 40: 361–379.PubMedCrossRefGoogle Scholar
  18. Burnashev N, Rozov A. 2000. Genomic control of receptor function. Cell Mol Life Sci 57: 1499–507.PubMedCrossRefGoogle Scholar
  19. Carroll RC, Beattie EC, Zastrow M, von Malenka RC. 2001. Role of AMPA receptor endocytosis in synaptic plasticity. Nat Rev Neurosci 2: 315–324.PubMedCrossRefGoogle Scholar
  20. Carvalho AL, Kameyama K, Huganir RL. 1999. Characterization of phosphorylation sites on the glutamate receptor 4 subunit of the AMPA receptors. J. Neurosci 19: 4748–4754.PubMedGoogle Scholar
  21. Casabona G, Knopfel T, Kuhn R, Gasparini F, Baumann P, et al. 1997. Expression and coupling to polyphosphoinositide hydrolysis of group I metabotropic glutamate receptors in early postnatal and adult rat brain. Eur J Neurosci 9: 12–17.PubMedCrossRefGoogle Scholar
  22. Catania MV, Landwehrmeyer GB, Testa CM, Standaert DG, Penney JB Jr., et al. 1994. Metabotropic glutamate receptors are differentially regulated during development. Neuroscience 61: 481–495.PubMedCrossRefGoogle Scholar
  23. Chazot PL, Stephenson FA. 1997. Molecular dissection of native mammalian forebrain NMDA receptors containing the NR1 C2 exon: Direct demonstration of NMDA receptors comprising NR1, NR2A, and NR2B subunits within the same cortex. J Neurochem 69: 2138–2144.PubMedCrossRefGoogle Scholar
  24. Chen BS, Braud S, Badger JD II, Isaac JTR, Roche KW. 2006. Regulation of NR1/NR2C N-methyl-D-aspartate (NMDA) receptors by phosphorylation. J Biol Chem 281: 16583–16590.PubMedCrossRefGoogle Scholar
  25. Cho K, Brown MW, Bashir ZI. 2002. Mechanisms and physiological role of enhancement of mGluR5 receptor function by group II mGlu receptor activation in rat perirhinal cortex. J Physiol 540: 895–906.PubMedCrossRefGoogle Scholar
  26. Cho K, Francis JC, Hirbec H, Dev K, Brown MW, et al. 2003. Regulation of kainate receptors by protein kinase C and metabotropic glutamate receptors. J Physiol 548(3): 723–730.PubMedCrossRefGoogle Scholar
  27. Chung HJ, Xia J, Scannevin RH, Zhang X, Huganir RL. 2000. Phosphorylation of the AMPA receptor subunit GluR2 differentially regulates its interaction with PDZ domain-containing proteins. J Neurosci 20: 7258–7267.PubMedGoogle Scholar
  28. Ciruela F, Giacometti A, McIlhinney RA. 1999. Functional regulation of metabotropic glutamate receptor type 1c: A role for phosphorylation in the desensitization of the receptor. FEBS Lett 462: 278–282.PubMedCrossRefGoogle Scholar
  29. Collingridge GL, Isaac JT, Wang YT. 2004. Receptor trafficking and synaptic plasticity. Nat Rev Neurosci 5: 952–962.PubMedCrossRefGoogle Scholar
  30. Conn PJ, Pinn JP. 1997. Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 37: 205–237.PubMedCrossRefGoogle Scholar
  31. Crump FT, Dillman KS, Craig AM. 2001. cAMP-dependent protein kinase mediates activity-regulated synaptic targeting of NMDA receptors. J Neurosci 21: 5079–5088.PubMedGoogle Scholar
  32. Cull-Candy S, Brickley S, Farrat M. 2001. NMDA receptor subunits: Diversity, development and disease. Curr Opin Neurobiol 11: 327–335.PubMedCrossRefGoogle Scholar
  33. Curtis DR, Phillis JW, Watkins JC. 1959. Chemical excitation of spinal neurones. Nature 183: 611–612.PubMedCrossRefGoogle Scholar
  34. Danbolt NC. 2001. Glutamate uptake. Prog Neurobiol 65: 1–105.PubMedCrossRefGoogle Scholar
  35. Darstein M, Petralia RS, Swanson GT, Wenthold RJ, Heinemann SF. 2003. Distribution of kainate receptor subunits at hippocampal mossy fiber synapses. J Neurosci 23: 8013–8019.PubMedGoogle Scholar
  36. Daw MI, Chittajallu R, Bortolotto ZA, Dev KK, Duprat F, et al. 2000. PDZ proteins interacting with C-terminal GluR2/3 are involved in a PKC-dependent regulation of AMPA receptors at hippocampal synapses. Neuron 28: 873–886.PubMedCrossRefGoogle Scholar
  37. De Blasi A, Conn PJ, Pin J, Nicoletti F. 2001. Molecular determinants of metabotropic glutamate receptor signalling. Trends Pharmacol Sci 22: 114–120.PubMedCrossRefGoogle Scholar
  38. Derkach V, Barria A, Soderling TR. 1999. Ca2+/calmodulin-kinase II enhances channel conductance of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors. Proc Natl Acad Sci USA 96: 3269–3274.PubMedCrossRefGoogle Scholar
  39. Dev KK, Nakajima Y, Kitano J, Braithwaite SP, Henley JM, et al. 2000. PICK1 interacts with and regulates PKC phosphorylation of mGLUR7. J Neurosci 20: 7252–7257.PubMedGoogle Scholar
  40. Dhami G, Ferguson SSG. 2006. Regulation of metabotropic glutamate receptor signalling desensitization and endocytosis. Pharmacol Ther 111: 260–271.PubMedCrossRefGoogle Scholar
  41. Dingledine R, Borges K, Bowie D, Traynelis SF. 1999. The glutamate receptor ion channels. Pharmacol Rev 51: 7–61.PubMedGoogle Scholar
  42. Ehlers MD, Tingley WG, Huganir RL. 1995. Regulated subcellular distribution of the NR1 subunit of the NMDA receptor. Science 269: 1734–1737.PubMedCrossRefGoogle Scholar
  43. Ehlers MD, Zhang S, Bernhadt JP, Huganir RL. 1996. Inactivation of NMDA receptors by direct interaction of calmodulin with the NR1 subunit. Cell 84: 745–755.PubMedCrossRefGoogle Scholar
  44. Elezgarai I, Benitez R, Mateos JM, Lazaro E, Osorio A, et al. 1999. Developmental expression of the group III metabotropic glutamate receptor mGluR4a in the medial nucleus of the trapezoid body of the rat. J Comp Neurol 411: 431–440.PubMedCrossRefGoogle Scholar
  45. Esteban JA, Shi SH, Wilson C, Nuriya M, Huganir RL, et al. 2003. PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity. Nat Neurosci 6: 136–143.PubMedCrossRefGoogle Scholar
  46. Fagni L, Ango F, Perroy J, Bockaert J. 2004. Identification and functional roles of metabotropic glutamate receptor-interacting proteins. Sem Cell Dev Biol 15: 289–298.CrossRefGoogle Scholar
  47. Fong DK, Rao A, Crump FT, Craig AM. 2002. Rapid synaptic remodeling by protein kinase C: Reciprocal translocation of NMDA receptors and calcium/calmodulin-dependent kinase II. J Neurosci 22: 2153–2164.PubMedGoogle Scholar
  48. Francesconi A, Duvoisin RM. 2000. Opposing effects of protein kinase C and protein kinase A on metabotropic glutamate receptor signaling: Selective desensitization of the inositol triphosphate/Ca pathway by phosphorylation of the receptor–G protein-coupling domain. Proc Natl Acad Sci USA 97: 6185–6190.PubMedCrossRefGoogle Scholar
  49. Gallyas F Jr., Ball SM, Molnár E. 2003. Assembly and cell surface expression of KA-2 subunit-containing kainate receptors. J Neurochem 86: 1414–1427.PubMedCrossRefGoogle Scholar
  50. Garcia EP, Mehta S, Blair LA, Wells DG, Shang J, et al. 1998. SAP90 binds and clusters kainate receptors causing incomplete desensitization. Neuron 21: 727-739.PubMedCrossRefGoogle Scholar
  51. Garcia-Gallo M, Renart J, Diaz-Guerra M. 2001. The NR1 subunit of the N-methyl-D-aspartate receptor can be effectively expressed alone in the cell surface of mammalian cells and is required for the transport of the NR2A subunit. Biochem J 356: 539–547.PubMedCrossRefGoogle Scholar
  52. Gereau RW, Heinemann SF. 1998. Role of protein kinase C phosphorylation in rapid desensitization of metabotropic glutamate receptor 5. Neuron 20: 143–151.PubMedCrossRefGoogle Scholar
  53. Golshani P, Warren RA, Jones EG. 1998. Progression of change in NMDA, non-NMDA, and metabotropic glutamate receptor function at the developing corticothalamic synapse. J Neurophysiol 80: 143–154.PubMedGoogle Scholar
  54. Groc L, Heine M, Cognet L, Brickley K, Stephenson FA, et al. 2004. Differential activity-dependent regulation of the lateral mobilities of AMPA and NMDA receptors. Nat Neurosci 7: 695–696.PubMedCrossRefGoogle Scholar
  55. Grosshans DR, Clayton DA, Coultrap SJ, Browning MD. 2002. LTP leads to rapid surface expression of NMDA but not AMPA receptors in adult rat CA1. Nat Neurosci 5: 27–33.PubMedCrossRefGoogle Scholar
  56. Guillaud L, Setou M, Hirokawa N. 2003. KIF17 dynamics and regulation of NR2B trafficking in hippocampal neurons. J Neurosci 23: 131–140.PubMedGoogle Scholar
  57. Hanley JG, Henley JM. 2005. PICK1 is a calcium-sensor for NMDA-induced AMPA receptor trafficking. EMBO J 24: 3266–3278.PubMedCrossRefGoogle Scholar
  58. Harris SL, Gallyas F, Molnár E. 2004. Activation of metabotropic glutamate receptors does not alter the phosphorylation state of GluR1 AMPA receptor subunit at serine 845 in perirhinal cortical neurons. Neurosci Lett 372: 132–136.PubMedCrossRefGoogle Scholar
  59. Hawkins LM, Chazot PL, Stephenson FA. 1999. Biochemical evidence for the co-association of three N-methyl-d-aspartate (NMDA) R2 subunits in recombinant NMDA receptors. J Biol Chem 274: 27211–27218.PubMedCrossRefGoogle Scholar
  60. Hayashi T. 1954. Effects of sodium glutamate on the nervous system. Keio J Med 3: 192–193.Google Scholar
  61. Hayashi T, Huganir RL. 2004. Tyrosine phosphorylation and regulation of the AMPA receptor by SRC family tyrosine kinases. J Neurosci 24: 6152-6160.PubMedCrossRefGoogle Scholar
  62. Hermans E, Challiss RAJ. 2001. Structural, signalling and regulatory properties of the group I metabotropic glutamate receptors: Prototypic family C G-protein-coupled receptors. Biochem J 359: 465–484.PubMedCrossRefGoogle Scholar
  63. Hirbee H, Francis JC, Lauri SE, Braithwaite SP, Coussen F, et al. 2003. Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP. Neuron 37: 625-638.CrossRefGoogle Scholar
  64. Hisatsune C, Umemori H, Inoue T, Michikawa T, Kohda K, et al. 1997. Phosphorylation-dependent regulation of N-methyl-D-aspartate receptors by calmodulin. J Biol Chem 272: 20805–20810.PubMedCrossRefGoogle Scholar
  65. Hollmann M. 1999. Molecular structure of ionotropic glutamate receptors. Handbook of Experimental Pharmacology. Ionotropic Glutamate Receptors in the CNS, Vol. 141.Jonas P, Monyer H, editors.Heidelberg: Springer.Google Scholar
  66. Hollmann M, Heinemann S. 1994. Cloned glutamate receptors. Ann Rev Neurosci 17: 31–108.PubMedCrossRefGoogle Scholar
  67. Hollmann M, Maron C, Heinemann S. 1994. N-glycosylation site tagging suggests a three transmembrane domain topology for the glutamate receptor GluR1. Neuron 13: 1331–1343.PubMedCrossRefGoogle Scholar
  68. Hollmann M, O'Shea-Greenfield A, Rogers SW, Heinemann S. 1989. Cloning by functional expression of a member of the glutamate receptor family. Nature 342: 643–648.PubMedCrossRefGoogle Scholar
  69. Houamed KM, Kuijper JL, Gilbert TL, Haldeman BA, O'Hara PJ, et al. 1991. Cloning, expression, and gene structure of a G-protein-coupled glutamate receptor from rat brain. Science 252: 1318–1321.PubMedCrossRefGoogle Scholar
  70. Huang YH, Bergles DE. 2004. Glutamate transporters bring competition to the synapse. Curr Opin Neurobiol 14: 346–352.PubMedCrossRefGoogle Scholar
  71. Hubert GW, Paquet M, Smith Y. 2001. Differential subcellular localization of mGluR1a and mGluR5 in the rat and monkey substantia nigra. J Neurosci 21: 1838–1847.PubMedGoogle Scholar
  72. Jaskolski F, Coussen F, Mulle C. 2005. Subcellular localization and trafficking of kainate receptors. Trends Pharmacol Sci 26: 20–26.PubMedCrossRefGoogle Scholar
  73. Jensen FE. 2005. Role of glutamate receptors in periventricular leucomalacia. J Child Neurol 20: 950–959.PubMedCrossRefGoogle Scholar
  74. Jo J, Ball SM, Seok H, Oh SB, Massey PV, et al. 2006. Experience-dependent modification of mechanisms of long-term depression. Nat Neurosci 9: 170–172.PubMedCrossRefGoogle Scholar
  75. Kieval JZ, Hubert GW, Charara A, Pare JF, Smith Y. 2001. Subcellular and subsynaptic localization of presynaptic and postsynaptic kainate receptor subunits in the monkey striatum. J Neurosci 21: 8746–8757.PubMedGoogle Scholar
  76. Kim CH, Braud S, Isaac JTR, Roche KW. 2005. Protein kinase C phosphorylation of the metabotropic glutamate receptor mGluR5 on serine 839 regulates Ca2+ oscillations. J Biol Chem 280(27): 25409–25415.PubMedCrossRefGoogle Scholar
  77. Konig N, Drian MJ, Manzoni O, Sladeczeck F. 1992. Early functional glutamate receptors in acutely dissociated embryonic raphe cells. Neuroreport 3: 738–740.PubMedCrossRefGoogle Scholar
  78. Kullmann DM. 2000. Spillover and synaptic cross talk mediated by glutamate and GABA in the mammalian brain. Prog Brain Res 125: 339–351.PubMedCrossRefGoogle Scholar
  79. Kumar SS, Bacci A, Kharazia V, Huguenard JR. 2002. A developmental switch of AMPA receptor subunits in neocortical pyramidal neurons. J Neurosci 22: 3005–3015.PubMedGoogle Scholar
  80. Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, et al. 2000. Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature 407: 971–977.PubMedCrossRefGoogle Scholar
  81. Lan JY, Skeberdis VA, Jover T, Grooms SY, Lin Y, et al. 2001a. Protein kinase C modulates NMDA receptor trafficking and gating. Nat Neurosci 4: 382–390.CrossRefGoogle Scholar
  82. Lan JY, Skeberdis VA, Jover T, Zheng X, Bennett MV, et al. 2001b. Activation of metabotropic glutamate receptor 1 accelerates NMDA receptor trafficking. J. Neurosci 21: 6058–6068.Google Scholar
  83. Lau LF, Huganir RL. 1995. Differential tyrosine phosphorylation of N-methyl-D-aspartate receptor subunits. J Biol Chem 270: 20036–20041.PubMedCrossRefGoogle Scholar
  84. Lee HK, Barbarosie M, Kameyama K, Bear MF, Huganir RL. 2000. Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity. Nature 405: 955–959.PubMedCrossRefGoogle Scholar
  85. Lee SH, Liu L, Wang YT, Sheng M. 2002. Clatrin adaptor AP2 and NSF interact with overlapping sites of GluR2 and plays distinct roles in AMPA receptor trafficking and hippocampal LTD. Neuron 36: 661–674.PubMedCrossRefGoogle Scholar
  86. Lei S, Czerwinska E, Czerwinski W, Walsh MP, McDonald JF. 2001. Regulation of NMDA receptor activity by F-actin and myosin light chain kinase. J Neurosci 21: 8464–8472.PubMedGoogle Scholar
  87. Leonard AS, Hell JW. 1997. Cyclic AMP-dependent protein kinase and protein kinase C phosphorylate N-methyl-D-aspartate receptors at different sites. J Biol Chem 272: 12107–12115.PubMedCrossRefGoogle Scholar
  88. Lerma J. 2003. Roles and rules of kainate receptors in synaptic transmission. Nat Rev Neurosci 4: 481–495.PubMedCrossRefGoogle Scholar
  89. Li B, Chen N, Luo T, Otsu Y, Murphy TH, et al. 2002. Differential regulation of synaptic and extra-synaptic NMDA receptors. Nat Neurosci 5: 833–834.PubMedCrossRefGoogle Scholar
  90. Li B, Otsu Y, Murphy TH, Raymond LA. 2003. Developmental decrease in NMDA receptor desensitization associated with shift to synapse and interaction with postsynaptic density-95. J Neurosci 23: 11244–11254.PubMedGoogle Scholar
  91. Liao GY, Wagner DA, Hsu MH, Leonard JP. 2001. Evidence for direct protein kinase-C mediated modulation of N-methyl-D-aspartate receptor current. Mol Pharmacol 59: 960–964.PubMedGoogle Scholar
  92. Lisman J. 1989. A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory. Proc Natl Acad Sci USA 86: 9574–9578.PubMedCrossRefGoogle Scholar
  93. Liu S-QJ, Cul-Candy SG. 2000. Synaptic activity at calcium-permeable AMPA receptors induces a switch in receptor subtype. Nature 405: 454–458.PubMedCrossRefGoogle Scholar
  94. Lopez-Bendito G, Shigemoto R, Fairen A, Lujan R. 2002. Differential distribution of group I metabotropic glutamate receptors during rat cortical development. Cereb Cortex 12: 625–638.PubMedCrossRefGoogle Scholar
  95. Lozovaya NA, Grebenyuk SE, Tsintsadze TS, Feng B, Monaghan DT, et al. 2004. Extrasynaptic NR2B and NR2D subunits of NMDA receptors shape ‘superslow’ afterburst EPSC in rat hippocampus. J Physiol 558: 451–463.PubMedCrossRefGoogle Scholar
  96. Lu W, Man H, Ju W, Trimble WS, Mac Donald JF, et al. 2001. Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons. Neuron 29: 243–254.PubMedCrossRefGoogle Scholar
  97. Lujan R, Roberts JDB, Shigemoto R, Ohishi H, Somogyi P, 1997. Differential plasma membrane distribution of metabotropic glutamate receptors mGluR1a, mGluR2 and mGluR5, relative to neurotransmitter release sites. J Chem Neuroanat 13: 219–241.PubMedCrossRefGoogle Scholar
  98. Luscher C, Xia H, Beattie EC, Carroll RC, von Zastrow M, et al. 1999. Role of AMPA receptor cycling in synaptic transmission and plasticity. Neuron 24: 649–658.PubMedCrossRefGoogle Scholar
  99. Luyt K, Váradi A, Molnár E. 2003. Functional metabotropic glutamate receptors are expressed in oligodendrocyte progenitor cells. J Neurochem 84: 1452–1464.PubMedCrossRefGoogle Scholar
  100. Luyt K, Váradi A, Durant CF, Molnár E. 2006. Oligodendroglial metabotropic glutamate receptors are developmentally regulated and involved in the prevention of apoptosis. J Neurochem 99: 641-656.PubMedCrossRefGoogle Scholar
  101. Mammen AL, Kemeyama K, Roche KW, Huganir RL. 1997. Phosphorylation of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit by calcium/calmodulin-dependent kinase II. J Biol Chem 272: 32528–32533.PubMedCrossRefGoogle Scholar
  102. Man HY, Wang Q, Lu WY, Ju W, Ahmadian G, et al. 2003. Activation of PI3-kinase is required for AMPA receptor insertion during LTP of mEPSCs in cultured hippocampal neurons. Neuron 38: 611–624.PubMedCrossRefGoogle Scholar
  103. Martin LJ, Furuta A, Blacktone CD. 1998. AMPA receptor protein in developing rat brain: Glutamate receptor-1 expression and localization change at regional, cellular, and subcellular levels with maturation. Neuroscience 83: 917–928.PubMedCrossRefGoogle Scholar
  104. Martin S, Henley JH. 2004. Activity-dependent endocytic sorting of kainate receptors to recycling or degradation pathways. EMBO J 23: 4749-4759.PubMedCrossRefGoogle Scholar
  105. Massey PV, Johnson BE, Moult PR, Auberson YP, Brown MW, et al. 2004. Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression. J Neurosci 24: 7821-7828.PubMedCrossRefGoogle Scholar
  106. Masu M, Tanade Y, Tsuchida K, Shigemoto R, Nakanishi S. 1991. Sequence and expression of a metabotropic glutamate receptor. Nature 349: 760–765.PubMedCrossRefGoogle Scholar
  107. Matsuda S, Mikawa S, Hirai H. 1999. Phosphorylation of serine-880 in GluR2 by protein kinase C prevents its C terminus from binding with glutamate receptor-interacting protein. J Neurochem 73: 1765–1768.PubMedCrossRefGoogle Scholar
  108. Mayer ML. 2005. Glutamate receptor ion channels. Curr Opin Neurobiol 15: 282–288.PubMedCrossRefGoogle Scholar
  109. Mayer ML, 2006. Glutamate receptors at atomic resolution. Nature 440: 456–462.PubMedCrossRefGoogle Scholar
  110. Mayer ML, Armstrong N. 2004. Structure and function of glutamate receptor ion channels. Annu Rev Physiol 66: 161–181.PubMedCrossRefGoogle Scholar
  111. Mayer ML, Westbrook GL, Guthrie PB. 1984. Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurons. Nature 309: 261–263.PubMedCrossRefGoogle Scholar
  112. McDonald BJ, Chung HJ, Huganir RL. 2001. Identification of protein kinase C phosphorylation sites within the AMPA receptor GluR2 subunit. Neuropharmacology 41: 672–679.PubMedCrossRefGoogle Scholar
  113. McIlhinney RAJ, Le Bourdellès B, Molnár E, Tricaud N, Streit P, et al. 1998. Assembly intracellular targeting and cell surface expression of the human N-methyl-D-aspartate receptor subunits NR1a and NR2A in transfected cells. Neuropharmacology 37: 1355–1367.PubMedCrossRefGoogle Scholar
  114. McIlhinney RAJ, Molnár E, Atack JR, Whiting PJ. 1996. Cell surface expression of the human N-ethyl-D-aspartate receptor subunit 1a requires the co-expression of the NR2A subunit in transfected cells. Neuroscience 70: 989–997.PubMedCrossRefGoogle Scholar
  115. Minakami R, Iida K, Hirakawa N, Sugiyama H. 1995. The expression of two splice variants of metabotropic glutamate receptor subtype 5 in the rat brain and neuronal cells during development. J Neurochem 65: 1536–1542.PubMedCrossRefGoogle Scholar
  116. Molnár E, Baude A, Richmond SA, Patel PB, Somogyi P, et al. 1993. Biochemical and immunocytochemical characterization of antipeptide antibodies to a cloned GluR1 glutamate receptor subunit: Cellular and subcellular distribution in the rat forebrain. Neuroscience 53: 307–326.PubMedCrossRefGoogle Scholar
  117. Molnár E, McIlhinney RAJ, Baude A, Nusser Z, Somogyi P. 1994. Membrane topology of the GluR1 glutamate receptor subunit: Epitope mapping by site-directed anti-peptide antibodies. J Neurochem 63: 683–693.PubMedCrossRefGoogle Scholar
  118. Molnár E, Varadi A, McIlhinney RAJ, Ashcroft SJH. 1995. Identification of functional ionotropic glutamate receptor proteins in pancreatic β-cells and islets of Langerhans. FEBS Lett 371: 253–257.PubMedCrossRefGoogle Scholar
  119. Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH. 1994. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12: 529–540.PubMedCrossRefGoogle Scholar
  120. Moon IS, Apperson ML, Kennedy MB, 1994. The major tyrosine-phosphorylated protein in the postsynaptic density fraction is N-methyl-D-aspartate receptor subunit 2B. Proc Natl Acad Sci USA 91: 3954–3958.PubMedCrossRefGoogle Scholar
  121. Moriyoshi K, Masu M, Ishii T, Shigemoto R, Mizuno N, et al. 1991. Molecular cloning and characterization of the rat NMDA receptor. Nature 354: 31–37.PubMedCrossRefGoogle Scholar
  122. Moult PR, Gladding CM, Sanderson TM, Fitzjohn SM, Bashir ZI, et al. 2006. Tyrosine phosphatases regulate AMPA receptor trafficking during metabotropic glutamate receptor-mediated long-term depression. J Neurosci 26: 2544–2554.PubMedCrossRefGoogle Scholar
  123. Nakagawa T, Cheng Y, Ramm E, Sheng M, Walz T. 2005. Structure and different conformational states of native AMPA receptor complexes. Nature 433: 545–549.PubMedCrossRefGoogle Scholar
  124. Nakajima Y, Yamamoto T, Nakayama T, Nakanishi S. 1999. A relationship between protein kinase C phosphorylation and calmodulin binding to the metabotropic glutamate receptor subtype 7. J Biol Chem 274: 27573–27577.PubMedCrossRefGoogle Scholar
  125. Nakazawa T, Komai S, Tezuka T, Hisatsune C, Umemori H, et al. 2001. Characterization of Fyn-mediated tyrosine phosphorylation sites on GluRepsilon 2 (NR2B) subunit of the N-methyl-D-aspartate receptor. J Biol Chem 276: 693–699.PubMedCrossRefGoogle Scholar
  126. Nasu-Nishimura Y, Hurtado D, Braud S, Tze-Tsang T, Isaac JTR, et al. 2006. Identification of an endoplasmic reticulum-retention motif in an intracellular loop of the kainate receptor subunit KA2. J Neurosci 26: 7014–7021.PubMedCrossRefGoogle Scholar
  127. Nicoletti F, Meek JL, Iadarola MJ, Chuang DM, Roth BL, et al. 1986. Coupling of inositol phospholipids metabolism with excitatory amino acid recognition sites in rat hippocampus. J Neurochem 46: 40–46.PubMedCrossRefGoogle Scholar
  128. Nicoll RA, Tomita S, Bredt DS. 2006. Auxiliary subunits assist AMPA-type glutamate receptors. Science 311: 1253–1256.PubMedCrossRefGoogle Scholar
  129. Nishimune A, Isaac JTR, Molnár E, Noël J, Nash SR, et al. 1998. NSF binding to GluR2 regulates synaptic transmission. Neuron 21: 87–97.PubMedCrossRefGoogle Scholar
  130. Noël J, Ralph GS, Pickard L, Williams J, Molnár E, et al. 1999. Surface expression of AMPA receptors in hippocampal neurons is regulated by an NSF-dependent mechanism. Neuron 23: 365–376.PubMedCrossRefGoogle Scholar
  131. Nong Y, Huang YQ, Ju W, Kalia LV, Ahmadian G, et al. 2003. Glycine binding primes NMDA receptor internalization. Nature 422: 302–307.PubMedCrossRefGoogle Scholar
  132. Nowak L, Bregestovski P, Ascher P, Herbet A, Prochiantz A. 1984. Magnesium gated glutamate-activated channels in mouse central neurons. Nature 307: 462–465.PubMedCrossRefGoogle Scholar
  133. Nusser Z, Lujan R, Laude G, Roberts JDB, Molnár E, et al. 1998. Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron 21: 545–559.PubMedCrossRefGoogle Scholar
  134. O'Connor V, El Far O, Bofill-Cardona E, Nanoff C, Freissmuth M, et al. 1999. Calmodulin dependence of presynaptic metabotropic glutamate receptor signalling. Science 286: 1180–1184.PubMedCrossRefGoogle Scholar
  135. Oh MC, Derkach VA, Guire ES, Soderling TS. 2006. Extrasynaptic membrane trafficking regulated by GluR1 serine 845 phosphorylation primes AMPA receptors for long-term potentiation. J Biol Chem 281: 752–758.PubMedCrossRefGoogle Scholar
  136. Omkumar RV, Kiely MJ, Rosenstein AJ, Min KT, Kennedy MB. 1996. Identification of a phosphorylation site for calcium/calmodulin dependent protein kinase II in the NR2B subunit of the N-methyl-D-aspartate receptor. J Biol Chem 271: 31670–31678.PubMedCrossRefGoogle Scholar
  137. Osten P, Khatri L, Perez JL, Kohr G, Giese G, et al. 2000. Mutagenesis reveals a role for ABP/GRIP binding to GluR2 in synaptic surface accumulation of the AMPA receptor, Neuron 27: 313–325.PubMedCrossRefGoogle Scholar
  138. Osten P, Srivastava S, Inman GJ, Vilim FS, Khatri L, et al. 1998. The AMPA receptor GluR2 C terminus can mediate a reversible, ATP-dependent interaction with NSF and alpha-and beta-SNAPs, Neuron 21: 99–110.PubMedCrossRefGoogle Scholar
  139. Passafaro M, Piech V, Sheng M. 2001. Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons. Nat Neurosci 4: 917–926.PubMedCrossRefGoogle Scholar
  140. Pérez-Otaño I, Lujan R, Tavalin ST, Plomann M, Modregger J, et al. 2006. Endocytosis and synaptic removal of NR3A-containing NMDA receptors by PACSIN1/synapsin1. Nat Neurosci 9: 611–621.PubMedCrossRefGoogle Scholar
  141. Petralia RS, Esteban JA, Wang YX, Partridge JG, Zhao HM, et al. 1999. Selective acquisition of AMPA receptors over postnatal development suggests a molecular basis for silent synapses. Nat Neurosci 2: 31–36.PubMedCrossRefGoogle Scholar
  142. Petralia RS, Wang YX, Wenthold RJ. 1994a. Histological and ultrastructural localization of the kainate receptor subunits, KA2 and GluR6/7, in the rat nervous system using selective antipeptide antibodies. J Comp Neurol 349: 85–110.CrossRefGoogle Scholar
  143. Petralia RS, Wang YX, Wenthold RJ. 1994c. The NMDA receptor subunits NR2A and NR2B show histological and ultrastructural localization patterns similar to those of NR1. J Neurosci 14: 6102–6120.Google Scholar
  144. Petralia RS, Yokotani N, Wenthold RJ. 1994b. Light and electron microscope distribution of the NMDA receptor subunit NMDAR1 in the rat nervous system using a selective anti-peptide antibody. J Neurosci 14: 667–696.Google Scholar
  145. Pickard L, Noël J, Duckworth JK, Fitzjohn SM, Henley JM, et al. 2001. Transient synaptic activation of NMDA receptors leads to the insertion of native AMPA receptors into hippocampal neuronal plasma membrane. Neuropharmacology 41: 700–713.PubMedCrossRefGoogle Scholar
  146. Pickard L, Noël J, Henley JM, Collingridge GL, Molnár E. 2000. Developmental changes in synaptic AMPA and NMDA receptor distribution and AMPA receptor subunit composition in living hippocampal neurons. J Neurosci 20: 7922–7931.PubMedGoogle Scholar
  147. Plant K, Pelkey KA, Bortolotto ZA, Morita D, Terashima A, et al. 2006. Transient incorporation of native GluR2-lacking AMPA receptors during hippocampal long-term potentiation. Nat Neurosci 9: 602–604.PubMedCrossRefGoogle Scholar
  148. Quinlan EM, Philpot BD, Huganir RL, Bear MF. 1999. Rapid, experience-dependent expression of synaptic NMDA receptors in visual cortex in vivo. Nat Neurosci 2: 352–357.PubMedCrossRefGoogle Scholar
  149. Racca C, Stephenson FA, Streit P, Roberts JDB, Somogyi P. 2000. NMDA receptor content of synapses in stratum radiatum of the hippocampal CA1 area. J Neurosci 20: 2512–2522.PubMedGoogle Scholar
  150. Raymond LA, Blackstone CD, Huganir RL. 1993. Phosphorylation and modulation of recombinant GluR6 glutamate receptors by cAMP-dependent protein kinase. Nature 361: 637–641.PubMedCrossRefGoogle Scholar
  151. Ren Z, Riley NJ, Garcia EP, Sanders JM, Swanson GT, et al. 2003. Multiple trafficking signals regulate kainate receptor KA2 subunit surface expression. J Neurosi 23: 6608–6616.Google Scholar
  152. Roche KW, O'Brien RJ, Mammen AL, Bernhardt J, Huganir RL. 1996. Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit. Neuron 16: 1179–1188.PubMedCrossRefGoogle Scholar
  153. Roche KW, Standley S, McCallum J, Dune Ly C, Ehlers MD, et al. 2001. Molecular determinants of NMDA receptor internalization. Nat Neurosci 4: 794–802.PubMedCrossRefGoogle Scholar
  154. Roche KW, Tu JC, Petralia RS, Xiao B, Wenthold RJ, et al. 1999. Homer 1b regulates the trafficking of group I metabotropic glutamate receptors. J Biol Chem 274: 25953–25957.PubMedCrossRefGoogle Scholar
  155. Romano C, Yang WL, O'Malley KL. 1996a. Metabotropic glutamate receptor 5 is a disulfide-linked dimmer. J Biol Chem 271: 28612–28616.CrossRefGoogle Scholar
  156. Romano C, van den Pol AN, O'Malley KL. 1996b, Enhanced early developmental expression of the metabotropic glutamate receptor mGluR5 in rat brain: Protein, mRNA splice variants, and regional distribution. J Comp Neurol 367: 403–412.CrossRefGoogle Scholar
  157. Romano C, Smout S, Miller JK, O'Malley KL. 2002. Developmental regulation of metabotropic glutamate receptor 5b protein in rodent brain. Neuroscience 111: 693–698.PubMedCrossRefGoogle Scholar
  158. Ruano D, Lambolez B, Rossier J, Paternain AV, Lerma J. 1995. Kainate receptor subunits expressed in single cultured hippocampal neurones: Molecular and functional variants by RNA editing. Neuron 14: 1009–1017.PubMedCrossRefGoogle Scholar
  159. Ruiz A, Sachidhanandam S, Utvik JK, Coussen F, Mulle C. 2005. Distinct subunits in heteromeric kainate receptors mediate ionotropic and metabotropic function at hippocampal mossy fiber synapses. J Neurosci 25: 11710–11718.PubMedCrossRefGoogle Scholar
  160. Sánchez-Pérez AM, Felipo V. 2005. Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms. Neurochem Int 47: 84–91.PubMedCrossRefGoogle Scholar
  161. Sasaki YF, Rothe T, Premkumar LS, Das S, Cui J, et al. 2002. Characterization and composition of the NR3A subunit of the NMDA receptor in recombinant systems and primary cortical neurons. J Neurophysiol 87: 2052–2063.PubMedGoogle Scholar
  162. Schoepp DD, Jane DE, Monn JA. 1999. Pharmacological agents acting at subtypes of metabotropic glutamate receptors. Neuropharmacology 38: 1431–1476.PubMedCrossRefGoogle Scholar
  163. Scott DB, Blanpied TA, Ehlers MD. 2003. Coordinated PKA and PKC phosphorylation suppresses RXR-mediated ER retention and regulates the surface delivery of NMDA receptors. Neuropharmacology 45: 755–767.PubMedCrossRefGoogle Scholar
  164. Seidenman KJ, Steinberg JP, Huganir R, Malinow R. 2003. Glutamate receptor subunit 2 serine 880 phosphorylation modulates synaptic transmission and mediates plasticity in CA1 pyramidal cells. J Neurosci 23: 9220–9228.PubMedGoogle Scholar
  165. Serge A, Fourgeaud L, Hemar A, Choquet D. 2002. Receptor activation and homer differentially control the lateral mobility of metabotropic glutamate receptor 5 in the neuronal membrane. J Neurosci 22: 3910–3920.PubMedGoogle Scholar
  166. Shen L, Liang F, Walensky LD, Huganir RL. 2000. Regulation of AMPA receptor GluR1 subunit surface expression by a 4.1N-linked actin cytoskeletal association. J Neurosci 20: 7932–7940.PubMedGoogle Scholar
  167. Shi S, Hayashi Y, Esteban JA, Malinow R. 2001. Subunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons. Cell 105: 331–343.PubMedCrossRefGoogle Scholar
  168. Shigemoto R, Kinoshita A, Wada E, Nomura S, Ohishi H, et al. 1997. Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. J Neurosci 17: 7503–7522.PubMedGoogle Scholar
  169. Shigemoto R, Kulik A, Roberts JD, Ohishi H, Nusser Z, et al. 1996. Target-cell-specific concentration of a metabotropic glutamate receptor in the presynaptic active zone Nature 381: 523–525.PubMedCrossRefGoogle Scholar
  170. Shigemoto R, Nakanishi S, Mizuno N. 1992. Distribution of the mRNA for a metabotropic glutamate receptor (mGluR1) in the central nervous system: An in situ hybridization study in adult and developing rat. J Comp Neurol 322: 121–135.PubMedCrossRefGoogle Scholar
  171. Skeberdis VA, Chevaleyre V, Lau CG, Goldberg JH, Pettit DL, et al. 2006. Protein kinase A regulates calcium permeability of NMDA receptors. Nat Neurosci 9: 501–510.PubMedCrossRefGoogle Scholar
  172. Skeberdis VA, Lan J, Zheng X, Zukin RS, Bennett MV. 2001. Insulin promotes rapid delivery of N-methyl-D-aspartate receptors to the cell surface by exocytosis. Proc Natl Acad Sci USA 98: 3561–3566.PubMedCrossRefGoogle Scholar
  173. Sladeczek F, Pin JP, Recasens M, Bockaert J, Weiss S. 1985. Glutamate stimulates inositol phosphate formation in striatal neurones. Nature 317: 717–719.PubMedCrossRefGoogle Scholar
  174. Smith TC, Wang LY, Howe JR. 1999. Distinct kainate receptor phenotypes in immature and mature mouse cerebellar granule cells. J. Physiol 517: 51–58.PubMedCrossRefGoogle Scholar
  175. Snyder EM, Philpot BD, Huber KM, Dong X, Fallon JR, et al. 2001. Internalization of ionotropic glutamate receptors in response to mGluR activation. Nat Neurosci 4: 1079–1085.PubMedCrossRefGoogle Scholar
  176. Standley S, Roche KW, McCallum J, Sans N, Wenthold RJ. 2000. PDZ domain suppression of an ER retention signal in NMDA receptor NR1 splice variants. Neuron 28: 887–898.PubMedCrossRefGoogle Scholar
  177. Steinberg JP, Takamiya K, Shen Y, Xia J, Rudio ME, et al. 2006. Targeted in vivo mutations of the AMPA receptor subunit GluR2 and its interacting protein PICK1 eliminate cerebellar long-term depression. Neuron 49: 845–860.PubMedCrossRefGoogle Scholar
  178. Stocca G, Vicini S. 1998. Increased contribution of NR2A subunit to synaptic NMDA receptors in developing rat cortical neurons J Physiol 507: 13–24.PubMedCrossRefGoogle Scholar
  179. Sun L, Margolis FL, Shipley MT, Lidow MS. 1998. Identification of a long variant of mRNA encoding the NR3 subunit of the NMDA receptor: Its regional distribution and developmental expression in the rat brain. FEBS Lett 441: 392–396.PubMedCrossRefGoogle Scholar
  180. Sun X, Zhao Y, Wolf ME. 2005. Dopamine receptor stimulation modulates AMPA receptor synaptic insertion in prefrontal cortex neurons. J Neurosci 25: 7342–7351.PubMedCrossRefGoogle Scholar
  181. Takumi Y, Ramírez-León V, Laake P, Rinvik E, Ottersen OP. 1999. Different modes of expression of AMPA and NMDA receptors in hippocampal synapses. Nat Neurosci 2: 618–624.PubMedCrossRefGoogle Scholar
  182. Tamaru Y, Nomura S, Mizuno N, Shigemoto R. 2001. Distribution of metabotropic glutamate receptor mGluR3 in the mouse CNS: Differential location relative to pre- and postsynaptic sites. Neuroscience 106: 481–503.PubMedCrossRefGoogle Scholar
  183. Tanaka J, Matsuzaki M, Tarusawa E, Momiyama A, Molnár E, et al. 2005. Number and density of AMPA receptors in single synapses in immature cerebellum. J Neurosci 25: 799–807.PubMedCrossRefGoogle Scholar
  184. Tang YP, Shimizu E, Dube GR, Rampon C, Kerchner GA, et al. 1999. Genetic enhancement of learning and memory in mice. Nature 401: 63–69.PubMedCrossRefGoogle Scholar
  185. Tarnawa I, Vizi ES. 1998. 2,3-Benzodiazepine AMPA antagonists. Restor Neurol Neurosci 13: 41–57.PubMedGoogle Scholar
  186. Terashima A, Cotton L, Dev KK, Meyer G, Zaman S, et al. 2004. Regulation of synaptic strength and AMPA receptor subunit composition by PICK1. J Neurosci 24: 5381–5390.PubMedCrossRefGoogle Scholar
  187. Tigaret CM, Thalhammer A, Rast GF, Specht CG, Auberson YP, et al. 2006. Subunit dependencies of N-methyl-D-aspartate (NMDA) receptor-induced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor internalization. Mol Pharmacol 69: 1251–1259.PubMedCrossRefGoogle Scholar
  188. Tingley WG, Ehlers MD, Kameyama K, Doherty C, Ptak JB, et al. 1997. Characterization of protein kinase A and protein kinase C phosphorylation of the N-methyl-D-aspartate receptor NR1 subunit using phosphorylation site-specific antibodies. J Biol Chem 272: 5157–5166.PubMedCrossRefGoogle Scholar
  189. Tönnes J, Stierli B, Cerletti C, Behrmann JT, Molnár E, et al. 1999. Regional distribution and developmental changes of GluR1-flop protein revealed by monoclonal antibody in rat brain. J Neurochem 73: 2195–2205.PubMedGoogle Scholar
  190. Tovar KR, Westbrook GL. 2002. Mobile NMDA receptors at hippocampal synapses. Neuron 34: 255–264.PubMedCrossRefGoogle Scholar
  191. Triller A, Choquet D. 2005. Surface trafficking of receptors between synaptic and extrasynaptic membranes: And yet they do move! Trends Neurosci 28: 133–139.PubMedCrossRefGoogle Scholar
  192. Tsuchiya D, Kunishima N, Kamiya N, Jingami H, Morikawa K. 2002. Structural views of the ligand-binding cores of a metabotropic glutamate receptor complexed with an antagonist and both glutamate and Gb3+. Proc Natl Acad Sci USA 99: 2660–2665.PubMedCrossRefGoogle Scholar
  193. Vissel B, Krupp JJ, Heinemann SF, Westbrook GL. 2001. A use-dependent tyrosine dephosphorylation of NMDA receptors is independent of ion flux. Nat Neurosci 4: 587–596.PubMedCrossRefGoogle Scholar
  194. Vizi ES. 2000. Role of high-affinity receptors and membrane transporters in nonsynaptic communication and drug action in the central nervous system. Pharmacol Rev 52: 63–89.PubMedGoogle Scholar
  195. Vizi ES, Mike Á. 2006. Nonsynaptic receptors for GABA and Glu. Curr Top Med Chem 6: 941–948.PubMedCrossRefGoogle Scholar
  196. Vizi ES, Mike A, Tarnawa I. 1996. 2,3 Benzodiazepines (GKI 52466 and analogs): Negative allosteric modulators of AMPA receptors. CNS Drug Rev 2: 91–126.CrossRefGoogle Scholar
  197. Wang LY, Taverna FA, Huang XP, Mac Donald JF, Hampson DR. 1993. Phosphorylation and modulation of a kainate receptor (GluR6) by cAMP-dependent protein kinase. Science 259: 1173–1175.PubMedCrossRefGoogle Scholar
  198. Washbourne P, Bennett JE, McAllister AK. 2002. Rapid recruitment of NMDA receptor transport packets to nascent synapses. Nat Neurosci 5: 751–759.PubMedGoogle Scholar
  199. Watanabe M. 1997. Developmental dynamics of gene expression for NMDA receptor channel. The Ionotropic Glutamate Receptors. Monaghan DT, Wenthold RJ, editors. Humana Press, New Jersey.Google Scholar
  200. Watkins JC, Jane DE. 2006. The glutamate story. Br J Pharmacol 147: S100–S108.PubMedCrossRefGoogle Scholar
  201. Wenthold RJ, Prybylowski K, Standley S, Sans N, Petralia RS. 2003. Trafficking of NMDA receptors. Annu Rev Pharmacol Toxicol 43: 335–358.PubMedCrossRefGoogle Scholar
  202. Winder DG, Conn PJ. 1996. Roles of metabotropic glutamate receptors in glial function and glial-neuronal communication. J Neurosci Res 46: 131–137.PubMedCrossRefGoogle Scholar
  203. Wu H, Nash JE, Zamarano P, Garner CC. 2002. Interaction of SAP97 with minus-end-directed actin motor myosin VI. Implications for AMPA receptor trafficking. J Biol Chem 277: 30928–30934.PubMedCrossRefGoogle Scholar
  204. Xiao MY, Zhou Q, Nicoll RA. 2001. Metabotropic glutamate receptor activation causes a rapid redistribution of AMPA receptors. Neuropharmacology 41: 664–671.PubMedCrossRefGoogle Scholar
  205. Yang M, Leonard JP. 2001. Identification of mouse NMDA receptor subunit NR2A C-terminal tyrosine sites phosphorylated by coexpression with v-Src. J Neurochem 77: 580–588.PubMedCrossRefGoogle Scholar

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  • E. Molnár

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