The Synaptic Protein Network Associated with Ionotropic Glutamate Receptors

  • H.-C. Kornau
  • P. H. Seeburg
  • M. B. Kennedy
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 141)


Heteromeric glutamate receptor (GluR) channels are integrated into larger protein complexes at specific synaptic locations via protein-interaction modules located at the C-terminal tails of the receptor subunits. Even though the ion-channel characteristics of N-methyl-D-aspartate receptors (NMDARs) and α — amino — 3 — hydroxy — 5 — methyl — 4 — isoxazolepropionic acid receptors (AMPARs) are well characterized, much of their cell biology and cell physiology have remained in the dark. The current search for proteins interacting with the major GluRs promises to unravel mechanisms of synapse targeting, clustering in the subsynaptic membrane and linkage to diverse intracellular signaling pathways. This area of research is rapidly evolving. Based on current data, NMDARs and AMPARs appear to be connected to different intracellular proteins. Some of the proteins associated with NMDARs and nonNMDARs have been identified, their corresponding cDNAs have been cloned and their relevance in the function of GluRs has been addressed.


AMPA Receptor Postsynaptic Density Ionotropic Glutamate Receptor NR2B Subunit NMDAR 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.


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  1. Andersen P, Figenschou Soleng A (1999) A thorny question: how does activity maintain dendritic spines? Nature Neurosci 2: 5–6PubMedCrossRefGoogle Scholar
  2. Aoki C, Fenstemaker S, Lubin M, Go CG (1993) Nitric oxide synthase in the visual cortex of monocular monkeys as revealed by light and electron microscopic immunocytochemistry. Brain Res 620: 97–113PubMedCrossRefGoogle Scholar
  3. Apperson ML, Moon I-S, Kennedy MB (1996) Characterization of densin-180, a new brain-specific synaptic protein of the 0-sialoglycoprotein family. J Neurosci 16: 6839–6852PubMedGoogle Scholar
  4. Barria A, Muller D, Derkach V, Griffith LC, Soderling TR (1997) Regulatory phosphorylation of AMPA type receptors by CaMKII during long-term potentiation. Science 276: 2042–2044PubMedCrossRefGoogle Scholar
  5. Bennett MK, Erondu NE, Kennedy MB (1983) Purification and characterization of a calmodulin-dependent protein kinase that is highly concentrated in brain. J Biol Chem 258: 12735–12744PubMedGoogle Scholar
  6. Bliss TVP, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361: 31–39PubMedCrossRefGoogle Scholar
  7. Blitzer RD, Connor JH, Brown GP, Wong T, Shenolikar S, Iyengar R, Landau EM (1998) Gating of CaMKII by cAMP-regulated protein phosphatase activity during LTP. Science 280: 1940–1942PubMedCrossRefGoogle Scholar
  8. Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE, Santillano DR, Wu Z, Huang F, Xia H, Peters MF, Froehner SC, Bredt DS (1996) Interaction of nitric-oxide synthase with the postsynaptic density protein PSD-95 and a-1-syntrophin mediated by PDZ domains. Cell 84: 757–767PubMedCrossRefGoogle Scholar
  9. Brenman JE,Topinka JR, Cooper EC, McGee AW, Rosen J, Milroy T, Ralston HJ, Bredt DS (1998) Localization of postsynaptic density-93 to dendritic microtubules and interaction with microtubule-associated protein 1 A. J Neurosci 18: 8805–8813Google Scholar
  10. Chen H-J, Kennedy MB (1997) Identification and cloning of a novel 130 kd protein containing a ras GTPase-activating domain from the rat forebrain postsynaptic density fraction. Abstr Soc Neurosci 23: 1466Google Scholar
  11. Chen H-J, Rojas-Soto M, Oguni A, Kennedy MB (1998) A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM Kinase II. Neuron 20: 895–904PubMedCrossRefGoogle Scholar
  12. Cho KO, Hunt CA, Kennedy MB (1992) The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein. Neuron 9: 929–942PubMedCrossRefGoogle Scholar
  13. Deguchi M, Hata Y, Takeuchi M, Ide N, Hirao K, Yao I, Irie M, Toyoda A, Takai Y (1998) BEGAIN (brain-enriched guanylate kinase-associated protein), a novel neuronal PSD-95/SAP90-binding protein. J Biol Chem 273: 26269–26272PubMedCrossRefGoogle Scholar
  14. 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: 279–284PubMedCrossRefGoogle Scholar
  15. Doyle DA, Lee A, Lewis J, Kim E, Sheng M, MacKinnon R (1996) Crystal structure of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ. Cell 85: 1067–1076PubMedCrossRefGoogle Scholar
  16. Durand G, Kovalchuk Y, Konnerth A (1996) Long term potentiation and functional synapse induction in developing hippocampus. Nature 381: 71–75.PubMedCrossRefGoogle Scholar
  17. Ebralidze AK, Rossi DJ, Tonegawa S, Slater NT (1996) Modification of NMDAR channels and synaptic transmission by targeted disruption of the NR2C gene. J Neurosci 16: 5014–5025PubMedGoogle Scholar
  18. Ehlers MD, Fung ET, O’Brien RJ, Huganir RL (1998) Splice variant-specific interaction of the NMDAR subunit NR1 with neuronal intermediate filaments. J Neurosci 18: 720–730PubMedGoogle Scholar
  19. Ehlers MD, Zhang S, Bernhadt JP, Huganir RL (1996b) Inactivation of NMDARs by direct interaction of calmodulin with the NR1 subunit. Cell 84: 745–755PubMedCrossRefGoogle Scholar
  20. English JD, Sweatt JD (1996) Activation of p42 mitogen-activated protein kinase in hippocampal long term potentiation. J Biol Chem 271: 24329–24332PubMedCrossRefGoogle Scholar
  21. Feng H-P, Gierasch LM (1998) Molecular chaperones: clamps for the Clps? Curr Biol 8: R464 - R467PubMedCrossRefGoogle Scholar
  22. Fields S, Song O (1989) A novel genetic system to detect protein-protein interactions. Nature 340: 245–246PubMedCrossRefGoogle Scholar
  23. Fields S, Sternglanz R (1994) The two-hybrid system: an assay for protein-protein interactions. Trends Genet 10: 286–292PubMedCrossRefGoogle Scholar
  24. Fukunaga K, Stoppini L, Miyamoto E, Muller D (1993) Long-term potentiation is associated with an increased activity of Ca’/calmodulin-dependent protein kinase II. J Biol Chem 268: 7863–7867PubMedGoogle Scholar
  25. Furuyashiki T, Fujisawa K, Fujita A, Madaule P, Uchino S, Mishina M, Bito H, Narumiya S (1999) Citron, a rho-target, interacts with PSD-95/SAP-90 at glutamatergic synapses in the thalamus. J Neurosci 19: 109–118PubMedGoogle Scholar
  26. Gallo V, Upson LM, Hayes WP, Vyklicky L, Winters CA, Buonanno A (1992) Molecular cloning and developmental analysis of a new glutamate receptor subunit isoform in cerebellum. J. Neurosci 12: 1010–1023PubMedGoogle Scholar
  27. Garcia EP, Mehta S, Blair LAC, Wells DG, Shang J, Fukushima T, Fallon JR, Garner CC, Marshall J (1998) SAP90 binds and clusters kainate receptors causing incomplete desensitization. Neuron 21: 727–739PubMedCrossRefGoogle Scholar
  28. Garthwaite H (1991) Glutamate, nitric oxide and cell—cell signalling in the nervous system. Trends Neurosci 14: 60–67PubMedCrossRefGoogle Scholar
  29. Geiger JRP, Melcher T, Koh DS, Sakmann B, Seeburg PH, Jonas P, Monyer H (1995) Relative abundance of subunit mRNAs determines gating and Ca’ permeability of AMPA receptors in principal neurons and interneurons in rat CNS. Neuron 15: 193–204PubMedCrossRefGoogle Scholar
  30. Goldenring JR, McGuire JS, DeLorenzo RJ (1984) Identification of the major postsynaptic density protein as homologous with the major calmodulin-binding subunit of a calmodulin-dependent protein kinase. J Neurochem 42: 10771084Google Scholar
  31. Grant SG, O’Dell TJ, Karl KA, Stein PL, Soriano P, Kandel ER (1992) Impaired longterm potentiation, spatial learning, and hippocampal development in fyn mutant mice. Science 258: 1903–1910PubMedCrossRefGoogle Scholar
  32. Hsueh YP, Kim E, Sheng M (1997) Disulfide-linked head-to-head multimerization in the mechanism of ion channel clustering by PSD-95. Neuron 18: 803–814PubMedCrossRefGoogle Scholar
  33. Ichtchenko K, Hata Y, Nguyen T, Ullrich B, Missler M, Moomaw C, Stidhof TC (1995)Google Scholar
  34. Neuroligin 1: a splice site-specific ligand for ß-Neurexins. Cell 81:435–443Google Scholar
  35. Irie M, Hata Y, Takeuchi M, Ichtchenko A, Toyoda A, Hirao K, Takai Y, Rosahl TWGoogle Scholar
  36. Sudhof TC (1997) Binding of neuroligins to PSD-95. Science 277:1511–1515 Isaac JT, Nicoll RA, Malenka RC (1995) Evidence for silent synapses: implications for the expression of LTP. Neuron 15: 427–434Google Scholar
  37. Jahn R (1998) Synaptic transmission: Two players team up for a new tune. Curr Biol 8: R856 — R858PubMedCrossRefGoogle Scholar
  38. Kashiwabuchi N, Ikeda K, Araki K, Hirano T, Shibuki K, Takayama C, Inoue Y, Kutsuwada T, Yagi T, Kang Y, Aizawa S, Mishina M (1995) Impairment of motor coordination, Purkinje cell synapse formation, and cerebellar long term depression in GluR2 82 mutant mice. Cell 81: 245–252PubMedCrossRefGoogle Scholar
  39. Keinänen K, Wisden W, Sommer B, Werner P, Herb A, Verdoorn TA, Sakmann B, Seeburg PH (1990) A family of AMPA-selective glutamate receptors. Science 249: 556–560PubMedCrossRefGoogle Scholar
  40. Kelly PT, McGuinness TL, Greengard P (1984) Evidence that the major postsynaptic density protein is a component of a Ca2+/calmodulin-dependent protein kinase. Proc Natl Acad Sci USA 81: 945–949PubMedCrossRefGoogle Scholar
  41. Kennedy MB (1995) Origin of PDZ (DHR, GLGF) domains. Trends Biochem Sci 20: 350–350PubMedCrossRefGoogle Scholar
  42. Kennedy MB (1998) Signal transduction molecules at the glutamatergic postsynaptic membrane. Brain Research Reviews 26: 243–257PubMedCrossRefGoogle Scholar
  43. Kennedy MB, Bennett MK, Bulleit RF, Erondu NE, Jennings VR, Miller SM, Molloy SS, Patton BL, Schenker LJ (1990) Structure and regulation of type II calcium/calmodulin-dependent protein kinase in central nervous system neurons. Cold Spring Harbour Sympos Quant Biol 55: 101–110CrossRefGoogle Scholar
  44. Kennedy MB, Bennett MK, Erondu NE (1983) Biochemical and immunochemical evidence that the “major postsynaptic density protein” is a subunit of a calmodulindependent protein kinase. Proc Natl Acad Sci USA 80: 7357–7361PubMedCrossRefGoogle Scholar
  45. The Synaptic Protein Network Associated with Ionotropic Glutamate Receptors 139Google Scholar
  46. Kim E, Cho KO, Rothschild A, Sheng M (1996) Heteromultimerization and NMDARclustering activity of chapsyn-110, a member of the PSD-95 family of proteins. Neuron 17: 103–113PubMedCrossRefGoogle Scholar
  47. Kim E, Naisbitt S, Hsueh YP, Rao. A, Rothschild A, Craig AM, Sheng M (1997) GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules. J Cell Biol 136: 669–678Google Scholar
  48. Kim JH, Liao D, Lau L-F, Huganir RL (1998) SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family. Neuron 20: 683–691PubMedCrossRefGoogle Scholar
  49. Kohr G, Seeburg PH (1996) Subtype-specific regulation of recombinant NMDARchannels by protein tyrosine kinases of the src family. J Physiol (Lond) 492: 445–452Google Scholar
  50. Kornau HC, Schenker LT, Kennedy MB, Seeburg PH (1995) Domain interaction between NMDAR subunits and the postsynaptic density protein PSD-95. Science 269: 1737–1740PubMedCrossRefGoogle Scholar
  51. Kornau HC, Seeburg PH, Kennedy MB (1997) Interaction of ion channels and receptors with PDZ domain proteins. Curr Opin Neurobiol 7: 368–373PubMedCrossRefGoogle Scholar
  52. Kurschner C, Mermelstein PG, Holden WT, Surmeier DJ (1998) CIPP, a novel multivalent PDZ domain protein, selectively interacts with Kir4.0 family members, NMDAR subunits, neurexins, and neuroligins. Mol Cell Neurosci 11: 161–172Google Scholar
  53. Kutsuwada T, Sakimura K, Manabe T, Takayama C, Katakura N, Kushiya E, Natsume R, Watanabe M, Inoue Y, Yagi T, Aizawa S, Arakawa M, Takahashi T, Nakamura Y, Mori H, Mishina M (1996) Impairment of suckling response, trigeminal neuronal pattern formation, and hippocampal LTD in NMDAR epsilon 2 subunit mutant mice. Neuron 16: 333–344PubMedCrossRefGoogle Scholar
  54. Landsend AS, Amiry-Moghaddam M, Matsubara A, Bergersen L, Usami S, Wenthold RJ, Ottersen OP (1997) Differential localization of delta GluRs in the rat cerebellum: coexpression with AMPA receptors in parallel fiber-spine synapses and absence from climbing fiber-spine synapses. J Neurosci 17: 834–842PubMedGoogle Scholar
  55. Lau LF, Huganir RL (1995) Differential tyrosine phosphorylation of N-methyl-Daspartate receptor subunits. J Biol Chem 270: 20036–20041PubMedCrossRefGoogle Scholar
  56. Leonard AS, Davare MA, Home MC, Garner CC, Hell JW (1998) SAP97 is associated with the (-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor G1uR1 subunit. J Biol Chem 273: 19518–19524PubMedCrossRefGoogle Scholar
  57. Liao D, Hessler NA, Malinow R (1995) Activation of postsynaptically silent synapses during pairing-induces LTP in CAl region of hippocampal slice. Nature 375: 400–404PubMedCrossRefGoogle Scholar
  58. Lin JW, Sheng M (1998) NSF and AMPA receptors get physical. Neuron 21: 267–270PubMedCrossRefGoogle Scholar
  59. Lin JW,Wyszynski M, Madhavan R, Sealock R, Kim JU, Sheng M (1998) Yotiao, a novel protein of neuromuscular junction and brain that interacts with specific splice vari-ants of NMDAR subunit NR1. J Neurosci 18: 2017–2027Google Scholar
  60. Lledo PM, Zhang X, Sudhof TC, Malenka RC, Nicoll RA (1998) Postsynaptic membrane fusion and long-term potentiation. Science 279: 399–403PubMedCrossRefGoogle Scholar
  61. Lomeli H, Wisden W, Köhler M, Keinänen K, Sommer B, Seeburg PH (1992) High- affinity kainate and domoate receptors in rat brain. FEBS Lett 307: 139–145PubMedCrossRefGoogle Scholar
  62. Lu YM, Roder JC, Davidow J, Salter MW (1998) Src activation in the induction of longterm potentiation in CAl hippocampal neurons. Science 279: 1363–1367PubMedCrossRefGoogle Scholar
  63. Madaule P, Eda M, Watanabe N, Fujisawa K, Matsuoka T, Bito H, Ishizaki T, Narumiya S (1998) Role of citron kinase as a target of the small GTPase Rho in cytokine-sis. Nature 394: 491–494PubMedCrossRefGoogle Scholar
  64. Madaule P, Furuyashiki T, Reid T, Ishizaki T, Watanabe G, Morii N, Narumiya S (1995)Google Scholar
  65. A novel partner for the GTP-bound forms of rho and rac. FEBS Lett 377:243–248Google Scholar
  66. Malinow R, Schulman H,Tsien RW (1989) Inhibition of post-synaptic PKC or CaMKII blocks induction but not expression of LTP. Science 245: 862–866PubMedGoogle Scholar
  67. Migaud M, Charlesworth P, Dempster M, Webster LC, Watabe AM, Makhinson M, He Y, Ramsay MF, Morris RG, Morrison JH, O’Dell TJ, Grant SG (1998) Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein [see comments]. Nature 396: 433–439PubMedCrossRefGoogle Scholar
  68. Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, Burnashev N, Sakmann B, Seeburg PH (1992) Heteromeric NMDARs: molecular and functional distinction of subtypes. Science 256: 1217–1221PubMedCrossRefGoogle Scholar
  69. 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: 3954–3958PubMedCrossRefGoogle Scholar
  70. Mori H, Manabe T, Watanabe M, Satoh Y, Suzuki N, Toki S, Nakamura K, Yagi T, Kushiya E, Takahashi T, Inoue Y, Sakimura K, Mishina M (1998) Role of the carboxy-terminal region of the GluRe2 subunit in synaptic localization of the NMDAR channel. Neuron 21: 571–580PubMedCrossRefGoogle Scholar
  71. Müller BM, Kistner U, Kindler S, Chung WJ, Kuhlendahl S, Fenster SD, Lau LF, Veh RW, Huganir RL, Gundelfinger ED, Garner CC (1996) SAP102, a novel postsynaptic protein that interacts with NMDAR complexes in vivo. Neuron 17: 255–265PubMedCrossRefGoogle Scholar
  72. Müller BM, Kistner U, Veh RW, Cases-Langhoff C, Becker B, Gundelfinger ED, Garner CG (1995) Molecular characterization and spatial distribution of SAP97, a novel presynaptic protein homologous to SAP90 and the Drosophila discs-large tumor suppressor protein. J Neurosci 15: 2354–2366PubMedGoogle Scholar
  73. Nguyen T, Sudhof TC (1997) Binding properties of neuroligin 1 and neurexin 1-beta reveal function as heterophilic cell adhesion molecules. J Biol Chem 272: 26032–26039PubMedCrossRefGoogle Scholar
  74. Niethammer M, Sheng M (1998) Identification of ion channel-associated proteins using the yeast two-hybrid system. Methods Enzymol 293: 104–122PubMedCrossRefGoogle Scholar
  75. Niethammer M, Kim E, Sheng M (1996) Interaction between the C terminus of NMDAR subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases. J Neurosci 16: 2157–2163PubMedGoogle Scholar
  76. Niethammer M, Valtschanoff JG, Kapoor TM, Allison DW, Weinberg TM, Craig AM, Sheng M (1998) CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90. Neuron 20: 693–707PubMedCrossRefGoogle Scholar
  77. Nishimune A, Isaac JTR, Molnar E, Joel J, Nash SR, Tagaya M, Collingridge GL, Nakanishi S, Henley JM (1998) NSF binding to G1uR2 regulates synaptic transmission. Neuron 21: 7–97CrossRefGoogle Scholar
  78. Omkumar RV, Kiely MJ, Rosenstein AJ, Min K-T, 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: 31670–31678PubMedCrossRefGoogle Scholar
  79. Osten P, Srivastava S, Imman GJ, Vilim FS, Khatri L, Lee LM, States BA, Einheber S, Milner TA, Hanson PI, et al (1998) The AMPA receptor G1uR2 C terminus can mediate a reversible, ATP-dependent interaction with NSF and alpha and beta SNAPs. Neuron 21: 99–110Google Scholar
  80. Ouyang Y, Kantor D, Harris KM, Schuman EM, Kennedy MB (1997) Visualization of the distribution of autophosphorylated calcium/calmodulin-dependent protein kinase II after tetanic stimulation in the CAl area of the hippocampus. J Neurosci 17: 5416–5427PubMedGoogle Scholar
  81. Ponting CP, Phillips C (1995) DHR (sic) domains in syntrophins, neuronal NO synthases and other intercellular proteins. Trends Biochem Sci 20: 102–103PubMedCrossRefGoogle Scholar
  82. Rao, A, Kim E, Sheng M, Craig AM (1998) Heterogeneity in the molecular composition of excitatory postsynaptic sites during development of hippocampal neurons in culture. J Neurosci 18: 1217–1229PubMedGoogle Scholar
  83. Roche KW, Ly CD, Petralia RS, Wang YX, McGee AW, Bredt DS, Wenthold RJ (1999) PSD-93 Interacts with the delta2 Glutamate Receptor Subunit at Parallel Fiber Synapses. J Neurosci (in press)Google Scholar
  84. Rodriguez-Moreno A, Lerma J (1998) Kainate receptor modulation of GABA release involves a metabotropic function. Neuron 20: 1211–1218PubMedCrossRefGoogle Scholar
  85. Rosenmund C, Westbrook GL (1993) Calcium-induced actin depolymerization reduces NMDA channel activity. Neuron 10: 805–814PubMedCrossRefGoogle Scholar
  86. Rothman JE (1994) Mechanisms of intracellular protein transport. Nature 372: 55–63PubMedCrossRefGoogle Scholar
  87. Sahyoun N, LeVine III H, McDonald OB, Cuatrecasas P (1986) Specific postsynaptic density proteins bind tubulin and calmodulin-dependent protein kinase type II.J Biol Chem 261: 12339–12344Google Scholar
  88. Sakimura K, Kutsuwada T, Ito I, Manabe T, Takayama C, Kushiya E, Yagi T, Aizawa S, Inoue Y, Sugiyama H, et al. (1995) Reduced hippocampal LTP and spatial learning in mice lacking NMDAR epsilon 1 subunit. Nature 373: 151–155PubMedCrossRefGoogle Scholar
  89. Seeburg PH, Higuchi M, Sprengel R (1998) RNA editing of brain glutamate receptor channels: mechanism and physiology. Brain Res Rev 267: 217–229CrossRefGoogle Scholar
  90. Shen K, Teruel MN, Subramanian K, Meyer T (1998) CaMKIlbeta functions as an F-actin targeting module that localizes CaMKIIalpha/beta heterooligomers to dendritic spines. Neuron 21: 593–606PubMedCrossRefGoogle Scholar
  91. Sheng M (1996) PDZs and receptor/channel clustering: rounding up the latest suspects [comment]. Neuron 17: 575–578PubMedCrossRefGoogle Scholar
  92. Song I, Kamboj S, Xia J, Dong H., Liao D, Huganir RL (1998) Interaction of the N-Google Scholar
  93. Ethylmaleimide-Sensitive Factor with AMPA Receptors. Neuron 21:393–400Google Scholar
  94. Sprengel R, Seeburg PH (1995) Ionotropic GluRs. In: Ligand-and voltage-gated ion channels, vol 2. CRC Press, Boca Raton, pp 213–263Google Scholar
  95. Sprengel R, Suchanek B, Amico C, Brusa R, Burnashev N, Rozov A, Hvalby O, Jensen V, Paulsen O, Andersen P, Kim JJ, Thompson RF, Sun W, Webster LC, Grant SG, Eilers J, Konnerth A, Li J, McNamara JO, Seeburg PH (1998) Importance of the intracellular domain of NR2 subunits for NMDAR function in vivo. Cell 92: 279–289PubMedCrossRefGoogle Scholar
  96. Srivastava S, Osten P, Vilim FS, Kathri L, Inman G, States B, Daly C, DeSouza S, Abagyan R, Valtschanoff JG, Weinberg RJ, Ziff EB (1998) Novel anchorage of G1uR2/3 to the postsynaptic density by the AMPA receptor-binding protein ABP. Neuron 21: 581–591PubMedCrossRefGoogle Scholar
  97. Staudinger J, Lu J, Olsen EN (1997) Specific interaction of the PDZ domain of the PDZ domain protein PICK1 with the COOH terminus of protein kinase C-alpha. J Biol Chem 172: 32019–32024CrossRefGoogle Scholar
  98. Staudinger J, Zhuo J, Burgess R, Elledge SJ, Olsen EN (1995) PICK1: a perinuclear binding protein and substrate for protein kinase C isolated by the yeast two-hybrid system. J Cell Biol 128: 263–271PubMedCrossRefGoogle Scholar
  99. Strack S, Colbran RJ (1998) Autophosphorylation-dependent targeting of calcium/ calmodulin-dependent protein kinase II by the NR2B subunit of the N-methylD-aspartate receptor. J Biol Chem 273: 20689–20692PubMedCrossRefGoogle Scholar
  100. Takeuchi M, Hata Y, Hirao K, Toyoda A, Irie M, Takai Y (1997) SAPAPs. A family of PSD-95/SAP90-associated proteins localized at postsynaptic density. J Biol Chem 272: 11943–11951PubMedCrossRefGoogle Scholar
  101. Tejedor FJ, Bokhari A, Rogero O, Gorczyca M, Zhang J, Kim E, Sheng M, Budnik V (1997) Essential role for dlg in synaptic clustering of Shaker K+ channels in vivo. J Neurosci 17: 152–159PubMedGoogle Scholar
  102. Ushkaryov YA, Petrenko AG, Geppert M, Sudhof TC (1992) Neurexins: synaptic cell surface proteins related to the alpha-latrotoxin receptor and laminin. Science 257: 50–56PubMedCrossRefGoogle Scholar
  103. Vissavajjhala P, Janssen WG, Hu Y, Gazzaley AH, Moran T, Hof PR, Morrison JH (1996) Synaptic distribution of the AMPA-G1uR2 subunit and its colocalization with calcium-binding proteins in rat cerebral cortex: an immunohistochemical study using a G1uR2-specific monoclonal antibody. Exp Neurol 142: 296–312PubMedCrossRefGoogle Scholar
  104. Wang Y, Durkin JP (1995) Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, but not N-methyl-D-aspartate, activates mitogen-activated protein kinase through G-protein beta gamma subunits in rat cortical neurons. J Biol Chem 270: 22783–22787PubMedCrossRefGoogle Scholar
  105. Wang Y, Small DL, Stanimirovic DB, Morley P, Durkin JP (1997) AMPA receptor-mediated regulation of a Gi-protein in cortical neurons. Nature 389: 502–504PubMedCrossRefGoogle Scholar
  106. Wang YT, Salter MW (1994) Regulation of NMDARs by tyrosine kinases and phos-phatases. Nature 369: 233–235PubMedCrossRefGoogle Scholar
  107. Wenthold RJ, Petralia RS, Blahos J, Niedzielski AS (1996) Evidence for multiple AMPA receptor complexes in hippocampal CA1/CA2 neurons. J Neurosci 16: 1982–1989PubMedGoogle Scholar
  108. Wigler MH (1990) GAPs in understanding Ras. Nature 346: 696–697PubMedCrossRefGoogle Scholar
  109. Wilding TJ, Huettner JE (1997) Activation and desensitization of hippocampal kainate receptors. J Neurosci 17: 2713–2721PubMedGoogle Scholar
  110. Wyszynski M, Lin J, Rao A, Nigh E, Beggs AH, Craig AM, Sheng M (1997) Competitive binding of alpha-actinin and calmodulin to the NMDAR. Nature 385: 439–442PubMedCrossRefGoogle Scholar
  111. Xia J, Zhang X, Staudinger J, Huganir RL (1999) Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1. Neuron 22: 179–187PubMedCrossRefGoogle Scholar
  112. Xia X, Dudek H, Miranti CK, Greenberg ME (1996) Calcium influx via the NMDAR induces immediate early gene transcription by a MAP kinase /ERK-dependent mechanism. J Neurosci 16: 5425–5436PubMedGoogle Scholar
  113. Yu XM, Askalan R, Keil GJ, 2nd, Salter MW (1997) NMDA channel regulation by channel-associated protein tyrosine kinase Src. Science 275: 674–678PubMedCrossRefGoogle Scholar
  114. Zhang S, Ehlers MD, Bernhardt JP, Su CT, Huganir RL (1998) Calmodulin mediates calcium-dependent inactivation of N-methyl-D-aspartate receptors. Neuron 21: 443–453PubMedCrossRefGoogle Scholar
  115. Zhang W, Vazquez L, Apperson M, Kennedy MB (1999) Citron binds to PSD-95 at glutamatergic synapses on inhibitory neurons in the hippocampus [in process citation]. J Neurosci 19: 96–108PubMedGoogle Scholar
  116. Ziff EB (1997) Enlightening the postsynaptic density. Neuron 19: 1163–1174PubMedCrossRefGoogle Scholar
  117. Zuo J, Dejager PL, Takahashi KA, Jiang WN, Linden, DJ, Heintz N (1997) Neurode-generation in lurcher mice caused by mutation in 82 gluatmate receptor gene.Nature 388: 769–773Google Scholar

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© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • H.-C. Kornau
  • P. H. Seeburg
  • M. B. Kennedy

There are no affiliations available

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