Metabotropic glutamate receptors and interacting proteins: Evolving drug targets

Current Drug Targets

Volumn 13, Issue 1, 2012, Pages 145-156

  Enz, Ralf ^a  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

Disease; G protein coupled receptor; Glutamate receptor; MGluR; Protein protein interaction; Signal transduction; Signaling complex; Structure

Indexed keywords

ADENOSINE A1 RECEPTOR; ADENOSINE A2 RECEPTOR; ALPHA ACTININ 4; ALPHA TUBULIN; BETA TUBULIN; CALCIUM SENSING RECEPTOR; CAVEOLIN; CAVEOLIN 1; FILAMIN A; METABOTROPIC RECEPTOR; METABOTROPIC RECEPTOR 1; METABOTROPIC RECEPTOR 2; METABOTROPIC RECEPTOR 3; METABOTROPIC RECEPTOR 4; METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR 6; METABOTROPIC RECEPTOR 7; METABOTROPIC RECEPTOR 8; MICROTUBULE ASSOCIATED PROTEIN 5; MU OPIATE RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 1; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2B; NEUROTRANSMITTER RECEPTOR; PROTEIN HOMER 1; PROTEIN HOMER 2; PROTEIN HOMER 3; REGULATOR PROTEIN; SEROTONIN 2A RECEPTOR; UNINDEXED DRUG; VIMENTIN;

ADDICTION; ALZHEIMER DISEASE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL FATE; DEPRESSION; DRUG TARGETING; EPILEPSY; HUMAN; HUNTINGTON CHOREA; MOLECULAR DYNAMICS; NERVE CELL NETWORK; NEUROTRANSMISSION; NONHUMAN; PARKINSON DISEASE; PROTEIN ASSEMBLY; PROTEIN DOMAIN; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REGULATORY MECHANISM; SCHIZOPHRENIA; SIGNAL TRANSDUCTION; SYNAPSE;

ANIMALS; DRUG DELIVERY SYSTEMS; EXCITATORY AMINO ACID AGENTS; HUMANS; PROTEIN BINDING; PROTEIN INTERACTION DOMAINS AND MOTIFS; RECEPTORS, METABOTROPIC GLUTAMATE; SIGNAL TRANSDUCTION;

EID: 84855828229     PISSN: 13894501     EISSN: 18735592     Source Type: Journal    
DOI: 10.2174/138945012798868452     Document Type: Article

References (189)

1. Bjarnadottir TK, Gloriam DE, Hellstrand SH, Kristiansson H, Fredriksson R, Schioth HB. Comprehensive repertoire and phylogenetic analysis of the G protein-coupled receptors in human and mouse. Genomics 2006; 88: 263-73.
2. Gloriam DE, Fredriksson R, Schioth HB. The G protein-coupled receptor subset of the rat genome. BMC Genomics 2007; 8: 338.
3. Harmar AJ, Hills RA, Rosser EM, et al. IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels. Nucleic Acids Res 2009; 37: D680-5.
4. Enz R. The trick of the tail: protein-protein interactions of metabotropic glutamate receptors. Bioessays 2007; 29: 60-73.
5. Ribeiro FM, Paquet M, Ferreira LT, et al. Metabotropic glutamate receptor-mediated cell signaling pathways are altered in a mouse model of Huntington's disease. J Neurosci 2010; 30: 316-24.
6. Tsai VW, Scott HL, Lewis RJ, Dodd PR. The role of group I metabotropic glutamate receptors in neuronal excitotoxicity in Alzheimer's disease. Neurotox Res 2005; 7: 125-41.
7. Johnson KA, Conn PJ, Niswender CM. Glutamate receptors as therapeutic targets for Parkinson's disease. CNS Neurol Disord Drug Targets 2009; 8: 475-91.
8. Gonzalez-Maeso J, Sealfon SC. Psychedelics and schizophrenia. Trends Neurosci 2009; 32: 225-32.
9. Sladeczek F, Pin JP, Recasens M, Bockaert J, Weiss S. Glutamate stimulates inositol phosphate formation in striatal neurones. Nature 1985; 317: 717-9.
10. Nicoletti F, Meek JL, Iadarola MJ, Chuang DM, Roth BL, Costa E. Coupling of inositol phospholipid metabolism with excitatory amino acid recognition sites in rat hippocampus. J Neurochem 1986; 46: 40-6.
11. Houamed KM, Kuijper JL, Gilbert TL, et al. Cloning, expression, and gene structure of a G protein-coupled glutamate receptor from rat brain. Science 1991; 252: 1318-21.
12. Masu M, Tanabe Y, Tsuchida K, Shigemoto R, Nakanishi S. Sequence and expression of a metabotropic glutamate receptor. Nature 1991; 349: 760-5.
13. Abe T, Sugihara H, Nawa H, Shigemoto R, Mizuno N, Nakanishi S. Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction. J Biol Chem 1992; 267: 13361-8.
14. Baude A, Nusser Z, Roberts JD, Mulvihill E, McIlhinney RA, Somogyi P. The metabotropic glutamate receptor (mGluR1 alpha) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron 1993; 11: 771-87.
15. Nusser Z, Mulvihill E, Streit P, Somogyi P. Subsynaptic segregation of metabotropic and ionotropic glutamate receptors as revealed by immunogold localization. Neuroscience 1994; 61: 421-7.
16. Lujan R, Roberts JD, Shigemoto R, Ohishi H, Somogyi P. Differential plasma membrane distribution of metabotropic glutamate receptors mGluR1 alpha, mGluR2 and mGluR5, relative to neurotransmitter release sites. J Chem Neuroanat 1997; 13: 219-41.
17. Tanabe Y, Nomura A, Masu M, Shigemoto R, Mizuno N, Nakanishi S. Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4. J Neurosci 1993; 13: 1372-8.
18. Ohishi H, Ogawa-Meguro R, Shigemoto R, Kaneko T, Nakanishi S, Mizuno N. Immunohistochemical localization of metabotropic glutamate receptors, mGluR2 and mGluR3, in rat cerebellar cortex. Neuron 1994; 13: 55-66.
19. Shigemoto R, Kinoshita A, Wada E, et al. Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. J Neurosci 1997; 17: 7503-22.
20. Shigemoto R, Kulik A, Roberts JD, et al. Target-cell-specific concentration of a metabotropic glutamate receptor in the presynaptic active zone. Nature 1996; 381: 523-5.
21. Nakajima Y, Iwakabe H, Akazawa C, et al. Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4-phosphonobutyrate. J Biol Chem 1993; 268: 11868-73.
22. Okamoto N, Hori S, Akazawa C, et al. Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction. J Biol Chem 1994; 269: 1231-6.
23. Duvoisin RM, Zhang C, Ramonell K. A novel metabotropic glutamate receptor expressed in the retina and olfactory bulb. J Neurosci 1995; 15: 3075-83.
24. Brandstätter JH, Koulen P, Kuhn R, van der Putten H, Wässle H. Compartmental localization of a metabotropic glutamate receptor (mGluR7): two different active sites at a retinal synapse. J Neurosci 1996; 16: 4749-56.
25. Takahashi T, Forsythe ID, Tsujimoto T, Barnes-Davies M, Onodera K. Presynaptic calcium current modulation by a metabotropic glutamate receptor. Science 1996; 274: 594-7.
26. Masugi M, Yokoi M, Shigemoto R, et al. Metabotropic glutamate receptor subtype 7 ablation causes deficit in fear response and conditioned taste aversion. J Neurosci 1999; 19: 955-63.
27. Masu M, Iwakabe H, Tagawa Y, et al. Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene. Cell 1995; 80: 757-65.
28. Vardi N, Duvoisin R, Wu G, Sterling P. Localization of mGluR6 to dendrites of ON bipolar cells in primate retina. J Comp Neurol 2000; 423: 402-12.
29. Ferraguti F, Shigemoto R. Metabotropic glutamate receptors. Cell Tissue Res 2006; 326: 483-504.
30. Mao LM, Liu XY, Zhang GC, et al. Phosphorylation of group I metabotropic glutamate receptors (mGluR1/5) in vitro and in vivo. Neuropharmacology 2008; 55: 403-8.
31. Kukhtina V, Kottwitz D, Strauss H, et al. Intracellular domain of nicotinic acetylcholine receptor: the importance of being unfolded. J Neurochem 2006; 97 Suppl 1: 63-7.
32. Seebahn A, Dinkel H, Mohrlüder J, et al. Structural characterization of intracellular C-terminal domains of group III metabotropic glutamate receptors. FEBS Lett 2011; 585: 511-6.
33. Cheng Y, LeGall T, Oldfield CJ, et al. Rational drug design via intrinsically disordered protein. Trends Biotechnol 2006; 24: 435-42.
34. Niswender CM, Conn PJ. Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 2010; 50: 295-322.
35. Chaudhari N, Pereira E, Roper SD. Taste receptors for umami: the case for multiple receptors. Am J Clin Nutr 2009; 90: 738S-42S.
36. Jong YJ, Kumar V, O'Malley KL. Intracellular metabotropic glutamate receptor 5 (mGluR5) activates signaling cascades distinct from cell surface counterparts. J Biol Chem 2009; 284: 35827-38.
37. Pellegrini-Giampietro DE. The distinct role of mGlu1 receptors in post-ischemic neuronal death. Trends Pharmacol Sci 2003; 24: 461-70.
38. Baskys A, Fang L, Bayazitov I. Activation of neuroprotective pathways by metabotropic group I glutamate receptors: a potential target for drug discovery? Ann N Y Acad Sci 2005; 1053: 55-73.
39. Tang FR, Bradford HF, Ling EA. Metabotropic glutamate receptors in the control of neuronal activity and as targets for development of anti-epileptogenic drugs. Curr Med Chem 2009; 16: 2189-204.
40. Bassell GJ, Warren ST. Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function. Neuron 2008; 60: 201-14.
41. Anjaneyulu M, Berent-Spillson A, Russell JW. Metabotropic glutamate receptors (mGluRs) and diabetic neuropathy. Curr Drug Targets 2008; 9: 85-93.
42. Fazio F, Notartomaso S, Aronica E, et al. Switch in the expression of mGlu1 and mGlu5 metabotropic glutamate receptors in the cerebellum of mice developing experimental autoimmune encephalomyelitis and in autoptic cerebellar samples from patients with multiple sclerosis. Neuropharmacology 2008; 55: 491-9.
43. Ferraguti F, Crepaldi L, Nicoletti F. Metabotropic glutamate 1 receptor: current concepts and perspectives. Pharmacol Rev 2008; 60: 536-81.
44. Maiese K, Chong ZZ, Shang YC, Hou J. Therapeutic promise and principles: Metabotropic glutamate receptors. Oxid Med Cell Longev 2008; 1: 1-14.
45. Dryja TP, McGee TL, Berson EL, et al. Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6. Proc Natl Acad Sci USA 2005; 102: 4884-9.
46. Koike C, Obara T, Uriu Y, et al. TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade. Proc Natl Acad Sci USA 2009;
47. Morgans CW, Zhang J, Jeffrey BG, et al. TRPM1 is required for the depolarizing light response in retinal ON-bipolar cells. Proc Natl Acad Sci USA 2009; 106: 19174-8.
48. Hagerman RJ, Berry-Kravis E, Kaufmann WE, et al. Advances in the treatment of fragile X syndrome. Pediatrics 2009; 123: 378-90.
49. Ciruela F, Canela L, Burgueno J, et al. Heptaspanning membrane receptors and cytoskeletal/scaffolding proteins: focus on adenosine, dopamine, and metabotropic glutamate receptor function. J Mol Neurosci 2005; 26: 277-92.
50. Doumazane E, Scholler P, Zwier JM, Eric T, Rondard P, Pin JP. A new approach to analyze cell surface protein complexes reveals specific heterodimeric metabotropic glutamate receptors. Faseb J 2011; 25: 66-77.
51. Kunishima N, Shimada Y, Tsuji Y, et al. Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature 2000; 407: 971-7.
52. Muto T, Tsuchiya D, Morikawa K, Jingami H. Structures of the extracellular regions of the group II/III metabotropic glutamate receptors. Proc Natl Acad Sci USA 2007; 104: 3759-64.
53. Gonzalez-Maeso J, Ang RL, Yuen T, et al. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 2008; 452: 93-7.
54. Cabello N, Gandia J, Bertarelli DC, et al. Metabotropic glutamate type 5, dopamine D2 and adenosine A2a receptors form higherorder oligomers in living cells. J Neurochem 2009; 109: 1497-507.
55. Renner M, Specht CG, Triller A. Molecular dynamics of postsynaptic receptors and scaffold proteins. Curr Opin Neurobiol 2008; 18: 532-40.
56. Cheng D, Hoogenraad CC, Rush J, et al. Relative and absolute quantification of postsynaptic density proteome isolated from rat forebrain and cerebellum. Mol Cell Proteomics 2006; 5: 1158-70.
57. Collins MO, Yu L, Coba MP, et al. Proteomic analysis of in vivo phosphorylated synaptic proteins. J Biol Chem 2005; 280: 5972-82.
58. Collins MO, Husi H, Yu L, et al. Molecular characterization and comparison of the components and multiprotein complexes in the postsynaptic proteome. J Neurochem 2006; 97 Suppl 1: 16-23.
59. Dosemeci A, Tao-Cheng JH, Vinade L, Jaffe H. Preparation of postsynaptic density fraction from hippocampal slices and proteomic analysis. Biochem Biophys Res Commun 2006; 339: 687-94.
60. Jordan BA, Fernholz BD, Boussac M, et al. Identification and verification of novel rodent postsynaptic density proteins. Mol Cell Proteomics 2004; 3: 857-71.
61. Li KW, Hornshaw MP, Van Der Schors RC, et al. Proteomics analysis of rat brain postsynaptic density. Implications of the diverse protein functional groups for the integration of synaptic physiology. J Biol Chem 2004; 279: 987-1002.
62. Liu SH, Cheng HH, Huang SY, Yiu PC, Chang YC. Studying the protein organization of the postsynaptic density by a novel solid phase-and chemical cross-linking-based technology. Mol Cell Proteomics 2006; 5: 1019-32.
63. Peng J, Kim MJ, Cheng D, Duong DM, Gygi SP, Sheng M. Semiquantitative proteomic analysis of rat forebrain postsynaptic density fractions by mass spectrometry. J Biol Chem 2004; 279: 21003-11.
64. Phillips GR, Florens L, Tanaka H, et al. Proteomic comparison of two fractions derived from the transsynaptic scaffold. J Neurosci Res 2005; 81: 762-75.
65. Schrimpf SP, Meskenaite V, Brunner E, et al. Proteomic analysis of synaptosomes using isotope-coded affinity tags and mass spectrometry. Proteomics 2005; 5: 2531-41.
66. Trinidad JC, Specht CG, Thalhammer A, Schoepfer R, Burlingame AL. Comprehensive identification of phosphorylation sites in postsynaptic density preparations. Mol Cell Proteomics 2006; 5: 914-22.
67. Trinidad JC, Thalhammer A, Specht CG, et al. Quantitative analysis of synaptic phosphorylation and protein expression. Mol Cell Proteomics 2008; 7: 684-96.
68. Yoshimura Y, Yamauchi Y, Shinkawa T, et al. Molecular constituents of the postsynaptic density fraction revealed by proteomic analysis using multidimensional liquid chromatographytandem mass spectrometry. J Neurochem 2004; 88: 759-68.
69. Croci C, Sticht H, Brandstätter JH, Enz R. Group I metabotropic glutamate receptors bind to protein phosphatase 1C. Mapping and modeling of interacting sequences. J Biol Chem 2003; 278: 50682-90.
70. Rose M, Dütting E, Schröder N, Sticht H, Brandstätter JH, Enz R. PNUTS forms a trimeric protein complex with GABA(C) receptors and protein phosphatase 1. Mol Cell Neurosci 2008; 37: 808-19.
71. Strack S, Kini S, Ebner FF, Wadzinski BE, Colbran RJ. Differential cellular and subcellular localization of protein phosphatase 1 isoforms in brain. J Comp Neurol 1999; 413: 373-84.
72. Bordelon JR, Smith Y, Nairn AC, Colbran RJ, Greengard P, Muly EC. Differential localization of protein phosphatase-1alpha, beta and gamma1 isoforms in primate prefrontal cortex. Cereb Cortex 2005; 15: 1928-37.
73. Szumlinski KK, Kalivas PW, Worley PF. Homer proteins: implications for neuropsychiatric disorders. Curr Opin Neurobiol 2006; 16: 251-7.
74. Bourgeron T. A synaptic trek to autism. Curr Opin Neurobiol 2009; 19: 231-4.
75. Hayashi MK, Tang C, Verpelli C, et al. The postsynaptic density proteins Homer and Shank form a polymeric network structure. Cell 2009; 137: 159-71.
76. Durand CM, Betancur C, Boeckers TM, et al. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet 2007; 39: 25-7.
77. Dev KK, Henley JM. The schizophrenic faces of PICK1. Trends Pharmacol Sci 2006; 27: 574-9.
78. Hong CJ, Liao DL, Shih HL, Tsai SJ. Association study of PICK1 rs3952 polymorphism and schizophrenia. Neuroreport 2004; 15: 1965-7.
79. Fujii K, Maeda K, Hikida T, et al. Serine racemase binds to PICK1: potential relevance to schizophrenia. Mol Psychiatry 2006; 11: 150-7.
80. Kang BS, Cooper DR, Jelen F, et al. PDZ tandem of human syntenin: crystal structure and functional properties. Structure 2003; 11: 459-68.
81. Im YJ, Park SH, Rho SH, et al. Crystal structure of GRIP1 PDZ6-peptide complex reveals the structural basis for class II PDZ target recognition and PDZ domain-mediated multimerization. J Biol Chem 2003; 278: 8501-7.
82. Barzik M, Carl UD, Schubert WD, Frank R, Wehland J, Heinz DW. The N-terminal domain of Homer/Vesl is a new class II EVH1 domain. J Mol Biol 2001; 309: 155-69.
83. Milligan G. G protein-coupled receptor hetero-dimerization: contribution to pharmacology and function. Br J Pharmacol 2009; 158: 5-14.
84. Bruno A, Guadix AE, Costantino G. Molecular dynamics simulation of the heterodimeric mGluR2/5HT(2A) complex. An atomistic resolution study of a potential new target in psychiatric conditions. J Chem Inf Model 2009; 49: 1602-16.
85. Brakeman PR, Lanahan AA, O'Brien R, et al. Homer: a protein that selectively binds metabotropic glutamate receptors. Nature 1997; 386: 284-8.
86. Kato A, Ozawa F, Saitoh Y, Hirai K, Inokuchi K. vesl, a gene encoding VASP/Ena family related protein, is upregulated during seizure, long-term potentiation and synaptogenesis. FEBS Lett 1997; 412: 183-9.
87. Shiraishi-Yamaguchi Y, Furuichi T. The Homer family proteins. Genome Biol 2007; 8: 206.
88. Tu JC, Xiao B, Yuan JP, et al. Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors. Neuron 1998; 21: 717-26.
89. Bockaert J, Perroy J, Becamel C, Marin P, Fagni L. GPCR interacting proteins (GIPs) in the nervous system: Roles in physiology and pathologies. Annu Rev Pharmacol Toxicol 2010; 50: 89-109.
90. Ciruela F, Soloviev MM, Chan WY, McIlhinney RA. Homer-1c/Vesl-1L modulates the cell surface targeting of metabotropic glutamate receptor type 1alpha: evidence for an anchoring function. Mol Cell Neurosci 2000; 15: 36-50.
91. Ango F, Pin JP, Tu JC, et al. Dendritic and axonal targeting of type 5 metabotropic glutamate receptor is regulated by homer1 proteins and neuronal excitation. J Neurosci 2000; 20: 8710-6.
92. Ango F, Prezeau L, Muller T, et al. Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer. Nature 2001; 411: 962-5.
93. Ango F, Robbe D, Tu JC, et al. Homer-dependent cell surface expression of metabotropic glutamate receptor type 5 in neurons. Mol Cell Neurosci 2002; 20: 323-9.
94. Roselli F, Hutzler P, Wegerich Y, Livrea P, Almeida OF. Disassembly of shank and homer synaptic clusters is driven by soluble beta-amyloid(1-40) through divergent NMDAR-dependent signalling pathways. PLoS One 2009; 4: e6011.
95. Beneken J, Tu JC, Xiao B, et al. Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition. Neuron 2000; 26: 143-54.
96. Kitano J, Kimura K, Yamazaki Y, et al. Tamalin, a PDZ domaincontaining protein, links a protein complex formation of group 1 metabotropic glutamate receptors and the guanine nucleotide exchange factor cytohesins. J Neurosci 2002; 22: 1280-9.
97. Hirose M, Kitano J, Nakajima Y, et al. Phosphorylation and recruitment of Syk by immunoreceptor tyrosine-based activation motif-based phosphorylation of tamalin. J Biol Chem 2004; 279: 32308-15.
98. Ogawa M, Miyakawa T, Nakamura K, et al. Altered sensitivities to morphine and cocaine in scaffold protein tamalin knockout mice. Proc Natl Acad Sci USA 2007; 104: 14789-94.
99. Sugi T, Oyama T, Muto T, Nakanishi S, Morikawa K, Jingami H. Crystal structures of autoinhibitory PDZ domain of Tamalin: implications for metabotropic glutamate receptor trafficking regulation. Embo J 2007; 26: 2192-205.
100. Kitano J, Yamazaki Y, Kimura K, Masukado T, Nakajima Y, Nakanishi S. Tamalin is a scaffold protein that interacts with multiple neuronal proteins in distinct modes of protein-protein association. J Biol Chem 2003; 278: 14762-8.
101. Carafoli E. Calcium-mediated cellular signals: a story of failures. Trends Biochem Sci 2004; 29: 371-9.
102. McNamara JO, Huang YZ, Leonard AS. Molecular signaling mechanisms underlying epileptogenesis. Sci STKE 2006; 2006: re12.
103. Park S, Park JM, Kim S, et al. Elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc/Arg3.1 essential for mGluR-LTD. Neuron 2008; 59: 70-83.
104. Lee JH, Lee J, Choi KY, et al. Calmodulin dynamically regulates the trafficking of the metabotropic glutamate receptor mGluR5. Proc Natl Acad Sci USA 2008; 105: 12575-80.
105. Minakami R, Jinnai N, Sugiyama H. Phosphorylation and calmodulin binding of the metabotropic glutamate receptor subtype 5 (mGluR5) are antagonistic in vitro. J Biol Chem 1997; 272: 20291-8.
106. Ishikawa K, Nash SR, Nishimune A, Neki A, Kaneko S, Nakanishi S. Competitive interaction of seven in absentia homolog-1A and Ca2+/calmodulin with the cytoplasmic tail of group 1 metabotropic glutamate receptors. Genes Cells 1999; 4: 381-90.
107. O'Connor V, El Far O, Bofill-Cardona E, et al. Calmodulin dependence of presynaptic metabotropic glutamate receptor signaling. Science 1999; 286: 1180-4.
108. Nakajima Y, Yamamoto T, Nakayama T, Nakanishi S. A relationship between protein kinase C phosphorylation and calmodulin binding to the metabotropic glutamate receptor subtype 7. J Biol Chem 1999; 274: 27573-7.
109. El Far O, Bofill-Cardona E, Airas JM, et al. Mapping of calmodulin and Gbetagamma binding domains within the Cterminal region of the metabotropic glutamate receptor 7A. J Biol Chem 2001; 276: 30662-9.
110. Airas JM, Betz H, El Far O. PKC phosphorylation of a conserved serine residue in the C-terminus of group III metabotropic glutamate receptors inhibits calmodulin binding. FEBS Lett 2001; 494: 60-3.
111. Sorensen SD, Macek TA, Cai Z, Saugstad JA, Conn PJ. Dissociation of protein kinase-mediated regulation of metabotropic glutamate receptor 7 (mGluR7) interactions with calmodulin and regulation of mGluR7 function. Mol Pharmacol 2002; 61: 1303-12.
112. Scheschonka A, Findlow S, Schemm R, et al. Structural determinants of calmodulin binding to the intracellular C-terminal domain of the metabotropic glutamate receptor 7A. J Biol Chem 2008; 283: 5577-88.
113. Ceulemans H, Bollen M. Functional diversity of protein phosphatase-1, a cellular economizer and reset button. Physiol Rev 2004; 84: 1-39.
114. Stamm S. Regulation of alternative splicing by reversible protein phosphorylation. J Biol Chem 2008; 283: 1223-7.
115. Shi Y. Serine/threonine phosphatases: mechanism through structure. Cell 2009; 139: 468-84.
116. Enz R. The metabotropic glutamate receptor mGluR7b binds to the catalytic gamma-subunit of protein phosphatase 1. J Neurochem 2002; 81: 1130-40.
117. Enz R, Croci C. Different binding motifs in metabotropic glutamate receptor type 7b for filamin A, protein phosphatase 1C, protein interacting with protein kinase C (PICK) 1 and syntenin allow the formation of multimeric protein complexes. Biochem J 2003; 372: 183-91.
118. Meiselbach H, Sticht H, Enz R. Structural analysis of the protein phosphatase 1 docking motif: molecular description of binding specificities identifies interacting proteins. Chem Biol 2006; 13: 49-59.
119. Corti C, Aldegheri L, Somogyi P, Ferraguti F. Distribution and synaptic localisation of the metabotropic glutamate receptor 4 (mGluR4) in the rodent CNS. Neuroscience 2002; 110: 403-20.
120. Schulz HL, Stohr H, Weber BH. Characterization of three novel isoforms of the metabotrobic glutamate receptor 7 (GRM7). Neurosci Lett 2002; 326: 37-40.
121. Valerio A, Ferraboli S, Paterlini M, Spano P, Barlati S. Identification of novel alternatively-spliced mRNA isoforms of metabotropic glutamate receptor 6 gene in rat and human retina. Gene 2001; 262: 99-106.
122. Sartorius LJ, Nagappan G, Lipska BK, et al. Alternative splicing of human metabotropic glutamate receptor 3. J Neurochem 2006; 96: 1139-48.
123. Malherbe P, Kratzeisen C, Lundstrom K, Richards JG, Faull RL, Mutel V. Cloning and functional expression of alternative spliced variants of the human metabotropic glutamate receptor 8. Brain Res Mol Brain Res 1999; 67: 201-10.
124. Tateyama M, Kubo Y. Coupling profile of the metabotropic glutamate receptor 1alpha is regulated by the C-terminal domain. Mol Cell Neurosci 2007; 34(3): 445-52.
125. Page G, Khidir FA, Pain S, et al. Group I metabotropic glutamate receptors activate the p70S6 kinase via both mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK 1/2) signaling pathways in rat striatal and hippocampal synaptoneurosomes. Neurochem Int 2006; 49: 413-21.
126. Perroy J, Prezeau L, De Waard M, Shigemoto R, Bockaert J, Fagni L. Selective blockade of P/Q-type calcium channels by the metabotropic glutamate receptor type 7 involves a phospholipase C pathway in neurons. J Neurosci 2000; 20: 7896-904.
127. Albasanz JL, Dalfo E, Ferrer I, Martin M. Impaired metabotropic glutamate receptor/phospholipase C signaling pathway in the cerebral cortex in Alzheimer's disease and dementia with Lewy bodies correlates with stage of Alzheimer's-disease-related changes. Neurobiol Dis 2005; 20: 685-93.
128. Mameli M, Balland B, Lujan R, Luscher C. Rapid synthesis and synaptic insertion of GluR2 for mGluR-LTD in the ventral tegmental area. Science 2007; 317: 530-3.
129. Aronica E, Gorter JA, Jansen GH, et al. Expression and cell distribution of group I and group II metabotropic glutamate receptor subtypes in taylor-type focal cortical dysplasia. Epilepsia 2003; 44: 785-95.
130. Ortiz P, Vanaclocha F, Lopez-Bran E, et al. Genetic analysis of the GRM1 gene in human melanoma susceptibility. Eur J Hum Genet 2007; 15: 1176-82.
131. Sillevis Smitt P, Kinoshita A, De Leeuw B, et al. Paraneoplastic cerebellar ataxia due to autoantibodies against a glutamate receptor. N Engl J Med 2000; 342: 21-7.
132. Coesmans M, Smitt PA, Linden DJ, et al. Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies. Ann Neurol 2003; 53: 325-36.
133. Valerio A, Ferrario M, Paterlini M, et al. Spinal cord mGlu1a receptors: possible target for amyotrophic lateral sclerosis therapy. Pharmacol Biochem Behav 2002; 73: 447-54.
134. Porter RH, Jaeschke G, Spooren W, et al. Fenobam: a clinically validated nonbenzodiazepine anxiolytic is a potent, selective, and noncompetitive mGlu5 receptor antagonist with inverse agonist activity. J Pharmacol Exp Ther 2005; 315: 711-21.
135. Oka A, Takashima S. The up-regulation of metabotropic glutamate receptor 5 (mGluR5) in Down's syndrome brains. Acta Neuropathol 1999; 97: 275-8.
136. Dalfo E, Albasanz JL, Rodriguez A, Martin M, Ferrer I. Abnormal group I metabotropic glutamate receptor expression and signaling in the frontal cortex in Pick disease. J Neuropathol Exp Neurol 2005; 64: 638-47.
137. Blumcke I, Becker AJ, Klein C, et al. Temporal lobe epilepsy associated up-regulation of metabotropic glutamate receptors: correlated changes in mGluR1 mRNA and protein expression in experimental animals and human patients. J Neuropathol Exp Neurol 2000; 59: 1-10.
138. Lee HG, Ogawa O, Zhu X, et al. Aberrant expression of metabotropic glutamate receptor 2 in the vulnerable neurons of Alzheimer's disease. Acta Neuropathol 2004; 107: 365-71.
139. Poulopoulou C, Davaki P, Koliaraki V, Kolovou D, Markakis I, Vassilopoulos D. Reduced expression of metabotropic glutamate receptor 2mRNA in T cells of ALS patients. Ann Neurol 2005; 58: 946-9.
140. de Quervain DJ, Papassotiropoulos A. Identification of a genetic cluster influencing memory performance and hippocampal activity in humans. Proc Natl Acad Sci USA 2006; 103: 4270-4.
141. Swanson CJ, Bures M, Johnson MP, Linden AM, Monn JA, Schoepp DD. Metabotropic glutamate receptors as novel targets for anxiety and stress disorders. Nat Rev Drug Discov 2005; 4: 131-44.
142. Schoepp DD, Wright RA, Levine LR, Gaydos B, Potter WZ. LY354740, an mGlu2/3 receptor agonist as a novel approach to treat anxiety/stress. Stress 2003; 6: 189-97.
143. Tang FR, Chia SC, Chen PM, et al. Metabotropic glutamate receptor 2/3 in the hippocampus of patients with mesial temporal lobe epilepsy, and of rats and mice after pilocarpine-induced status epilepticus. Epilepsy Res 2004; 59: 167-80.
144. Geurts JJ, Wolswijk G, Bo L, et al. Expression patterns of Group III metabotropic glutamate receptors mGluR4 and mGluR8 in multiple sclerosis lesions. J Neuroimmunol 2005; 158: 182-90.
145. Zeitz C, van Genderen M, Neidhardt J, et al. Mutations in GRM6 cause autosomal recessive congenital stationary night blindness with a distinctive scotopic 15-Hz flicker electroretinogram. Invest Ophthalmol Vis Sci 2005; 46: 4328-35.
146. Friedman RA, Van Laer L, Huentelman MJ, et al. GRM7 variants confer susceptibility to age-related hearing impairment. Hum Mol Genet 2009; 18: 785-96.
147. Ganda C, Schwab SG, Amir N, et al. A family-based association study of DNA sequence variants in GRM7 with schizophrenia in an Indonesian population. Int J Neuropsychopharmacol 2009; 12: 1283-9.
148. Ohtsuki T, Koga M, Ishiguro H, et al. A polymorphism of the metabotropic glutamate receptor mGluR7 (GRM7) gene is associated with schizophrenia. Schizophr Res 2008; 101: 9-16.
149. Shibata H, Tani A, Chikuhara T, et al. Association study of polymorphisms in the group III metabotropic glutamate receptor genes, GRM4 and GRM7, with schizophrenia. Psychiatry Res 2009; 167: 88-96.
150. Scherer SW, Duvoisin RM, Kuhn R, Heng HH, Belloni E, Tsui LC. Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q. Genomics 1996; 31: 230-3.
151. Scherer SW, Soder S, Duvoisin RM, Huizenga JJ, Tsui LC. The human metabotropic glutamate receptor 8 (GRM8) gene: a disproportionately large gene located at 7q31.3-q32.1. Genomics 1997; 44: 232-6.
152. Francesconi A, Kumari R, Zukin RS. Proteomic analysis reveals novel binding partners of metabotropic glutamate receptor 1. J Neurochem 2009; 108: 1515-25.
153. Cabello N, Remelli R, Canela L, et al. Actin-binding protein alphaactinin-1 interacts with the metabotropic glutamate receptor type 5b and modulates the cell surface expression and function of the receptor. J Biol Chem 2007; 282: 12143-53.
154. Rose M, Dütting E, Enz R. Band 4.1 proteins are expressed in the retina and interact with both isoforms of the metabotropic glutamate receptor type 8. J Neurochem 2008;
155. Lu D, Yan H, Othman T, Rivkees SA. Cytoskeletal protein 4.1G is a binding partner of the metabotropic glutamate receptor subtype 1 alpha. J Neurosci Res 2004; 78: 49-55.
156. Enz R. The actin-binding protein Filamin-A interacts with the metabotropic glutamate receptor type 7. FEBS Lett 2002; 514: 184-8.
157. Moritz A, Scheschonka A, Beckhaus T, Karas M, Betz H. Metabotropic glutamate receptor 4 interacts with microtubuleassociated protein 1B. Biochem Biophys Res Commun 2009; 390: 82-6.
158. Saugstad JA, Yang S, Pohl J, Hall RA, Conn PJ. Interaction between metabotropic glutamate receptor 7 and alpha tubulin. J Neurochem 2002; 80: 980-8.
159. Ciruela F, Robbins MJ, Willis AC, McIlhinney RA. Interactions of the C terminus of metabotropic glutamate receptor type 1alpha with rat brain proteins: evidence for a direct interaction with tubulin. J Neurochem 1999; 72: 346-54.
160. Ciruela F, Escriche M, Burgueno J, et al. Metabotropic glutamate 1alpha and adenosine A1 receptors assemble into functionally interacting complexes. J Biol Chem 2001; 276: 18345-51.
161. Ferre S, Karcz-Kubicha M, Hope BT, et al. Synergistic interaction between adenosine A2A and glutamate mGlu5 receptors: implications for striatal neuronal function. Proc Natl Acad Sci USA 2002; 99: 11940-5.
162. Gama L, Wilt SG, Breitwieser GE. Heterodimerization of calcium sensing receptors with metabotropic glutamate receptors in neurons. J Biol Chem 2001; 276: 39053-9.
163. Burgueno J, Canela EI, Mallol J, Lluis C, Franco R, Ciruela F. Mutual regulation between metabotropic glutamate type 1alpha receptor and caveolin proteins: from traffick to constitutive activity. Exp Cell Res 2004; 300: 23-34.
164. Tabata T, Araishi K, Hashimoto K, et al. Ca2+ activity at GABAB receptors constitutively promotes metabotropic glutamate signaling in the absence of GABA. Proc Natl Acad Sci USA 2004; 101: 16952-7.
165. Rives ML, Vol C, Fukazawa Y, et al. Crosstalk between GABA(B) and mGlu1a receptors reveals new insight into GPCR signal integration. EMBO J 2009; 28: 2195-208.
166. Tsuji Y, Shimada Y, Takeshita T, et al. Cryptic dimer interface and domain organization of the extracellular region of metabotropic glutamate receptor subtype 1. J Biol Chem 2000; 275: 28144-51.
167. Romano C, Miller JK, Hyrc K, et al. Covalent and noncovalent interactions mediate metabotropic glutamate receptor mGlu5 dimerization. Mol Pharmacol 2001; 59: 46-53.
168. Perroy J, Raynaud F, Homburger V, et al. Direct interaction enables cross-talk between ionotropic and group I metabotropic glutamate receptors. J Biol Chem 2008; 283: 6799-805.
169. Schröder H, Wu DF, Seifert A, et al. Allosteric modulation of metabotropic glutamate receptor 5 affects phosphorylation, internalization, and desensitization of the micro-opioid receptor. Neuropharmacology 2009; 56: 768-78.
170. Kitano J, Nishida M, Itsukaichi Y, et al. Direct interaction and functional coupling between metabotropic glutamate receptor subtype 1 and voltage-sensitive Cav2.1 Ca2+ channel. J Biol Chem 2003; 278: 25101-8.
171. Zhang J, Cheng S, Xiong Y, et al. A novel association of mGluR1a with the PDZ scaffold protein CAL modulates receptor activity. FEBS Lett 2008; 582: 4117-24.
172. Cheng S, Zhang J, Zhu P, et al. The PDZ domain protein CAL interacts with mGluR5a and modulates receptor expression. J Neurochem 2010; 112: 588-98.
173. Hirbec H, Perestenko O, Nishimune A, et al. The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes. Analysis of PDZ binding motifs. J Biol Chem 2002; 277: 15221-4.
174. Paquet M, Asay MJ, Fam SR, et al. The PDZ scaffold NHERF-2 interacts with mGluR5 and regulates receptor activity. J Biol Chem 2006; 281: 29949-61.
175. Dev KK, Nakajima Y, Kitano J, Braithwaite SP, Henley JM, Nakanishi S. PICK1 interacts with and regulates PKC phosphorylation of mGLUR7. J Neurosci 2000; 20: 7252-7.
176. El Far O, Airas J, Wischmeyer E, Nehring RB, Karschin A, Betz H. Interaction of the C-terminal tail region of the metabotropic glutamate receptor 7 with the protein kinase C substrate PICK1. Eur J Neurosci 2000; 12: 4215-21.
177. Ferreira LT, Dale LB, Ribeiro FM, Babwah AV, Pampillo M, Ferguson SS. Calcineurin inhibitor protein (CAIN) attenuates Group I metabotropic glutamate receptor endocytosis and signaling. J Biol Chem 2009; 284: 28986-94.
178. Calo L, Bruno V, Spinsanti P, et al. Interactions between ephrin-B and metabotropic glutamate 1 receptors in brain tissue and cultured neurons. J Neurosci 2005; 25: 2245-54.
179. Piccinin S, Cinque C, Calo L, et al. Interaction between Ephrins and mGlu5 metabotropic glutamate receptors in the induction of long-term synaptic depression in the hippocampus. J Neurosci 2010; 30: 2835-43.
180. Dhami GK, Babwah AV, Sterne-Marr R, Ferguson SS. Phosphorylation-independent regulation of metabotropic glutamate receptor 1 signaling requires g protein-coupled receptor kinase 2 binding to the second intracellular loop. J Biol Chem 2005; 280: 24420-7.
181. Bertaso F, Lill Y, Airas JM, et al. MacMARCKS interacts with the metabotropic glutamate receptor type 7 and modulates G proteinmediated constitutive inhibition of calcium channels. J Neurochem 2006; 99: 288-98.
182. Canela L, Fernandez-Duenas V, Albergaria C, et al. The association of metabotropic glutamate receptor type 5 with the neuronal Ca2+-binding protein 2 modulates receptor function. J Neurochem 2009; 111: 555-67.
183. Wang H, Westin L, Nong Y, et al. Norbin is an endogenous regulator of metabotropic glutamate receptor 5 signaling. Science 2009; 326: 1554-7.
184. Anborgh PH, Godin C, Pampillo M, et al. Inhibition of metabotropic glutamate receptor signaling by the huntingtinbinding protein optineurin. J Biol Chem 2005; 280: 34840-8.
185. Tang Z, El Far O, Betz H, Scheschonka A. Pias1 interaction and sumoylation of metabotropic glutamate receptor 8. J Biol Chem 2005; 280: 38153-9.
186. Dütting E, Schröder-Kreß N, Sticht H, Enz R. Sumo E3 ligases are expressed in the retina and regulate sumoylation of the metabotropic glutamate receptor 8b. Biochem J 2011; 435: 365-71.
187. Cai Z, Saugstad JA, Sorensen SD, et al. Cyclic AMP-dependent protein kinase phosphorylates group III metabotropic glutamate receptors and inhibits their function as presynaptic receptors. J Neurochem 2001; 78: 756-66.
188. Flajolet M, Rakhilin S, Wang H, et al. Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3. Proc Natl Acad Sci USA 2003; 100: 16006-11.
189. Seebahn A, Rose M, Enz R. RanBPM is expressed in synaptic layers of the mammalian retina and binds to metabotropic glutamate receptors. FEBS Lett 2008; 582: 2453-7.