Logo of biochemjBJ Latest papers and much more!
Biochem J. 2001 Nov 1; 359(Pt 3): 465–484.
PMCID: PMC1222168

Structural, signalling and regulatory properties of the group I metabotropic glutamate receptors: prototypic family C G-protein-coupled receptors.


In 1991 a new type of G-protein-coupled receptor (GPCR) was cloned, the type 1a metabotropic glutamate (mGlu) receptor, which, despite possessing the defining seven-transmembrane topology of the GPCR superfamily, bore little resemblance to the growing number of other cloned GPCRs. Subsequent studies have shown that there are eight mammalian mGlu receptors that, together with the calcium-sensing receptor, the GABA(B) receptor (where GABA is gamma-aminobutyric acid) and a subset of pheromone, olfactory and taste receptors, make up GPCR family C. Currently available data suggest that family C GPCRs share a number of structural, biochemical and regulatory characteristics, which differ markedly from those of the other GPCR families, most notably the rhodopsin/family A GPCRs that have been most widely studied to date. This review will focus on the group I mGlu receptors (mGlu1 and mGlu5). This subgroup of receptors is widely and differentially expressed in neuronal and glial cells within the brain, and receptor activation has been implicated in the control of an array of key signalling events, including roles in the adaptative changes needed for long-term depression or potentiation of neuronal synaptic connectivity. In addition to playing critical physiological roles within the brain, the mGlu receptors are also currently the focus of considerable attention because of their potential as drug targets for the treatment of a variety of neurological and psychiatric disorders.

Full Text

The Full Text of this article is available as a PDF (548K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Dingledine R, Borges K, Bowie D, Traynelis SF. The glutamate receptor ion channels. Pharmacol Rev. 1999 Mar;51(1):7–61. [PubMed]
  • Sladeczek F, Pin JP, Récasens M, Bockaert J, Weiss S. Glutamate stimulates inositol phosphate formation in striatal neurones. Nature. 1985 Oct 24;317(6039):717–719. [PubMed]
  • Nicoletti F, Iadarola MJ, Wroblewski JT, Costa E. Excitatory amino acid recognition sites coupled with inositol phospholipid metabolism: developmental changes and interaction with alpha 1-adrenoceptors. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1931–1935. [PMC free article] [PubMed]
  • Sugiyama H, Ito I, Hirono C. A new type of glutamate receptor linked to inositol phospholipid metabolism. Nature. 1987 Feb 5;325(6104):531–533. [PubMed]
  • Houamed KM, Kuijper JL, Gilbert TL, Haldeman BA, O'Hara PJ, Mulvihill ER, Almers W, Hagen FS. Cloning, expression, and gene structure of a G protein-coupled glutamate receptor from rat brain. Science. 1991 May 31;252(5010):1318–1321. [PubMed]
  • Masu M, Tanabe Y, Tsuchida K, Shigemoto R, Nakanishi S. Sequence and expression of a metabotropic glutamate receptor. Nature. 1991 Feb 28;349(6312):760–765. [PubMed]
  • Conn PJ, Pin JP. Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol. 1997;37:205–237. [PubMed]
  • Aiba A, Chen C, Herrup K, Rosenmund C, Stevens CF, Tonegawa S. Reduced hippocampal long-term potentiation and context-specific deficit in associative learning in mGluR1 mutant mice. Cell. 1994 Oct 21;79(2):365–375. [PubMed]
  • Aiba A, Kano M, Chen C, Stanton ME, Fox GD, Herrup K, Zwingman TA, Tonegawa S. Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice. Cell. 1994 Oct 21;79(2):377–388. [PubMed]
  • Conquet F, Bashir ZI, Davies CH, Daniel H, Ferraguti F, Bordi F, Franz-Bacon K, Reggiani A, Matarese V, Condé F, et al. Motor deficit and impairment of synaptic plasticity in mice lacking mGluR1. Nature. 1994 Nov 17;372(6503):237–243. [PubMed]
  • Jia Z, Lu Y, Henderson J, Taverna F, Romano C, Abramow-Newerly W, Wojtowicz JM, Roder J. Selective abolition of the NMDA component of long-term potentiation in mice lacking mGluR5. Learn Mem. 1998 Sep-Oct;5(4-5):331–343. [PMC free article] [PubMed]
  • Lu YM, Jia Z, Janus C, Henderson JT, Gerlai R, Wojtowicz JM, Roder JC. Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP. J Neurosci. 1997 Jul 1;17(13):5196–5205. [PubMed]
  • Ichise T, Kano M, Hashimoto K, Yanagihara D, Nakao K, Shigemoto R, Katsuki M, Aiba A. mGluR1 in cerebellar Purkinje cells essential for long-term depression, synapse elimination, and motor coordination. Science. 2000 Jun 9;288(5472):1832–1835. [PubMed]
  • Pellicciari R, Costantino G. Metabotropic G-protein-coupled glutamate receptors as therapeutic targets. Curr Opin Chem Biol. 1999 Aug;3(4):433–440. [PubMed]
  • Schoepp DD, Jane DE, Monn JA. Pharmacological agents acting at subtypes of metabotropic glutamate receptors. Neuropharmacology. 1999 Oct;38(10):1431–1476. [PubMed]
  • Pin JP, De Colle C, Bessis AS, Acher F. New perspectives for the development of selective metabotropic glutamate receptor ligands. Eur J Pharmacol. 1999 Jun 30;375(1-3):277–294. [PubMed]
  • Chebib M, Johnston GA. The 'ABC' of GABA receptors: a brief review. Clin Exp Pharmacol Physiol. 1999 Nov;26(11):937–940. [PubMed]
  • Brown EM, MacLeod RJ. Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev. 2001 Jan;81(1):239–297. [PubMed]
  • Herrada G, Dulac C. A novel family of putative pheromone receptors in mammals with a topographically organized and sexually dimorphic distribution. Cell. 1997 Aug 22;90(4):763–773. [PubMed]
  • Ryba NJ, Tirindelli R. A new multigene family of putative pheromone receptors. Neuron. 1997 Aug;19(2):371–379. [PubMed]
  • Bockaert J, Pin JP. Molecular tinkering of G protein-coupled receptors: an evolutionary success. EMBO J. 1999 Apr 1;18(7):1723–1729. [PMC free article] [PubMed]
  • Costantino G, Macchiarulo A, Pellicciari R. Homology model of the closed, functionally active, form of the amino terminal domain of mGlur1. Bioorg Med Chem. 2001 Apr;9(4):847–852. [PubMed]
  • De Blasi A, Conn PJ, Pin J, Nicoletti F. Molecular determinants of metabotropic glutamate receptor signaling. Trends Pharmacol Sci. 2001 Mar;22(3):114–120. [PubMed]
  • O'Hara PJ, Sheppard PO, Thøgersen H, Venezia D, Haldeman BA, McGrane V, Houamed KM, Thomsen C, Gilbert TL, Mulvihill ER. The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins. Neuron. 1993 Jul;11(1):41–52. [PubMed]
  • Takahashi K, Tsuchida K, Tanabe Y, Masu M, Nakanishi S. Role of the large extracellular domain of metabotropic glutamate receptors in agonist selectivity determination. J Biol Chem. 1993 Sep 15;268(26):19341–19345. [PubMed]
  • Tones MA, Bendali N, Flor PJ, Knöpfel T, Kuhn R. The agonist selectivity of a class III metabotropic glutamate receptor, human mGluR4a, is determined by the N-terminal extracellular domain. Neuroreport. 1995 Dec 29;7(1):117–120. [PubMed]
  • Malitschek B, Schweizer C, Keir M, Heid J, Froestl W, Mosbacher J, Kuhn R, Henley J, Joly C, Pin JP, et al. The N-terminal domain of gamma-aminobutyric Acid(B) receptors is sufficient to specify agonist and antagonist binding. Mol Pharmacol. 1999 Aug;56(2):448–454. [PubMed]
  • Bräuner-Osborne H, Jensen AA, Sheppard PO, O'Hara P, Krogsgaard-Larsen P. The agonist-binding domain of the calcium-sensing receptor is located at the amino-terminal domain. J Biol Chem. 1999 Jun 25;274(26):18382–18386. [PubMed]
  • Hammerland LG, Krapcho KJ, Garrett JE, Alasti N, Hung BC, Simin RT, Levinthal C, Nemeth EF, Fuller FH. Domains determining ligand specificity for Ca2+ receptors. Mol Pharmacol. 1999 Apr;55(4):642–648. [PubMed]
  • Quiocho FA, Ledvina PS. Atomic structure and specificity of bacterial periplasmic receptors for active transport and chemotaxis: variation of common themes. Mol Microbiol. 1996 Apr;20(1):17–25. [PubMed]
  • Costantino G, Pellicciari R. Homology modeling of metabotropic glutamate receptors. (mGluRs) structural motifs affecting binding modes and pharmacological profile of mGluR1 agonists and competitive antagonists. J Med Chem. 1996 Sep 27;39(20):3998–4006. [PubMed]
  • Jensen AA, Sheppard PO, O'Hara PJ, Krogsgaard-Larsen P, Bräuner-Osborne H. The role of Arg(78) in the metabotropic glutamate receptor mGlu(1) for agonist binding and selectivity. Eur J Pharmacol. 2000 Jun 2;397(2-3):247–253. [PubMed]
  • Lin FF, Varney M, Sacaan AI, Jachec C, Daggett LP, Rao S, Flor P, Kuhn R, Kerner JA, Standaert D, et al. Cloning and stable expression of the mGluR1b subtype of human metabotropic receptors and pharmacological comparison with the mGluR5a subtype. Neuropharmacology. 1997 Jul;36(7):917–931. [PubMed]
  • Brabet I, Mary S, Bockaert J, Pin JP. Phenylglycine derivatives discriminate between mGluR1- and mGluR5-mediated responses. Neuropharmacology. 1995 Aug;34(8):895–903. [PubMed]
  • Han G, Hampson DR. Ligand binding to the amino-terminal domain of the mGluR4 subtype of metabotropic glutamate receptor. J Biol Chem. 1999 Apr 9;274(15):10008–10013. [PubMed]
  • Okamoto T, Sekiyama N, Otsu M, Shimada Y, Sato A, Nakanishi S, Jingami H. Expression and purification of the extracellular ligand binding region of metabotropic glutamate receptor subtype 1. J Biol Chem. 1998 May 22;273(21):13089–13096. [PubMed]
  • Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K. Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature. 2000 Oct 26;407(6807):971–977. [PubMed]
  • Galvez T, Parmentier ML, Joly C, Malitschek B, Kaupmann K, Kuhn R, Bittiger H, Froestl W, Bettler B, Pin JP. Mutagenesis and modeling of the GABAB receptor extracellular domain support a venus flytrap mechanism for ligand binding. J Biol Chem. 1999 May 7;274(19):13362–13369. [PubMed]
  • Peltekova V, Han G, Soleymanlou N, Hampson DR. Constraints on proper folding of the amino terminal domains of group III metabotropic glutamate receptors. Brain Res Mol Brain Res. 2000 Mar 10;76(1):180–190. [PubMed]
  • Hu J, Hauache O, Spiegel AM. Human Ca2+ receptor cysteine-rich domain. Analysis of function of mutant and chimeric receptors. J Biol Chem. 2000 May 26;275(21):16382–16389. [PubMed]
  • Kaupmann K, Huggel K, Heid J, Flor PJ, Bischoff S, Mickel SJ, McMaster G, Angst C, Bittiger H, Froestl W, et al. Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors. Nature. 1997 Mar 20;386(6622):239–246. [PubMed]
  • Gether U. Uncovering molecular mechanisms involved in activation of G protein-coupled receptors. Endocr Rev. 2000 Feb;21(1):90–113. [PubMed]
  • Albasanz JL, Ros M, Martín M. Characterization of metabotropic glutamate receptors in rat C6 glioma cells. Eur J Pharmacol. 1997 May 12;326(1):85–91. [PubMed]
  • Hudtloff C, Thomsen C. Autoradiographic visualization of group III metabotropic glutamate receptors using [3H]-L-2-amino-4-phosphonobutyrate. Br J Pharmacol. 1998 Jul;124(5):971–977. [PMC free article] [PubMed]
  • Mutel V, Adam G, Chaboz S, Kemp JA, Klingelschmidt A, Messer J, Wichmann J, Woltering T, Richards JG. Characterization of (2S,2'R,3'R)-2-(2',3'-[3H]-dicarboxycyclopropyl)glycine binding in rat brain. J Neurochem. 1998 Dec;71(6):2558–2564. [PubMed]
  • Schaffhauser H, Richards JG, Cartmell J, Chaboz S, Kemp JA, Klingelschmidt A, Messer J, Stadler H, Woltering T, Mutel V. In vitro binding characteristics of a new selective group II metabotropic glutamate receptor radioligand, [3H]LY354740, in rat brain. Mol Pharmacol. 1998 Feb;53(2):228–233. [PubMed]
  • Hinoi E, Ogita K, Takeuchi Y, Ohashi H, Maruyama T, Yoneda Y. Direct radiolabeling by [3H]quisqualic acid of group I metabotropic glutamate receptor in rat brain synaptic membranes. Brain Res. 2000 Oct 27;881(2):199–203. [PubMed]
  • Olah GA, Trakhanov S, Trewhella J, Quiocho FA. Leucine/isoleucine/valine-binding protein contracts upon binding of ligand. J Biol Chem. 1993 Aug 5;268(22):16241–16247. [PubMed]
  • Litschig S, Gasparini F, Rueegg D, Stoehr N, Flor PJ, Vranesic I, Prézeau L, Pin JP, Thomsen C, Kuhn R. CPCCOEt, a noncompetitive metabotropic glutamate receptor 1 antagonist, inhibits receptor signaling without affecting glutamate binding. Mol Pharmacol. 1999 Mar;55(3):453–461. [PubMed]
  • Coughlin SR. How the protease thrombin talks to cells. Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11023–11027. [PMC free article] [PubMed]
  • Hermans E, Nahorski SR, Challiss RA. Reversible and non-competitive antagonist profile of CPCCOEt at the human type 1alpha metabotropic glutamate receptor. Neuropharmacology. 1998 Dec;37(12):1645–1647. [PubMed]
  • Carroll FY, Stolle A, Beart PM, Voerste A, Brabet I, Mauler F, Joly C, Antonicek H, Bockaert J, Müller T, et al. BAY36-7620: a potent non-competitive mGlu1 receptor antagonist with inverse agonist activity. Mol Pharmacol. 2001 May;59(5):965–973. [PMC free article] [PubMed]
  • Gasparini F, Lingenhöhl K, Stoehr N, Flor PJ, Heinrich M, Vranesic I, Biollaz M, Allgeier H, Heckendorn R, Urwyler S, et al. 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology. 1999 Oct;38(10):1493–1503. [PubMed]
  • Mutel V, Ellis GJ, Adam G, Chaboz S, Nilly A, Messer J, Bleuel Z, Metzler V, Malherbe P, Schlaeger EJ, et al. Characterization of [(3)H]Quisqualate binding to recombinant rat metabotropic glutamate 1a and 5a receptors and to rat and human brain sections. J Neurochem. 2000 Dec;75(6):2590–2601. [PubMed]
  • Pagano A, Ruegg D, Litschig S, Stoehr N, Stierlin C, Heinrich M, Floersheim P, Prezèau L, Carroll F, Pin JP, et al. The non-competitive antagonists 2-methyl-6-(phenylethynyl)pyridine and 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester interact with overlapping binding pockets in the transmembrane region of group I metabotropic glutamate receptors. J Biol Chem. 2000 Oct 27;275(43):33750–33758. [PubMed]
  • Bräuner-Osborne H, Jensen AA, Krogsgaard-Larsen P. Interaction of CPCCOEt with a chimeric mGlu1b and calcium sensing receptor. Neuroreport. 1999 Dec 16;10(18):3923–3925. [PubMed]
  • Hammerland LG, Garrett JE, Hung BC, Levinthal C, Nemeth EF. Allosteric activation of the Ca2+ receptor expressed in Xenopus laevis oocytes by NPS 467 or NPS 568. Mol Pharmacol. 1998 Jun;53(6):1083–1088. [PubMed]
  • Jensen AA, Spalding TA, Burstein ES, Sheppard PO, O'Hara PJ, Brann MR, Krogsgaard-Larsen P, Bräuner-Osborne H. Functional importance of the Ala(116)-Pro(136) region in the calcium-sensing receptor. Constitutive activity and inverse agonism in a family C G-protein-coupled receptor. J Biol Chem. 2000 Sep 22;275(38):29547–29555. [PubMed]
  • Sladeczek F, Manzoni O, Fagni L, Dumuis A, Pin JP, Sebben M, Bockaert J. The metabotropic glutamate receptor (MGR): pharmacology and subcellular location. J Physiol Paris. 1992;86(1-3):47–55. [PubMed]
  • Thomsen C, Mulvihill ER, Haldeman B, Pickering DS, Hampson DR, Suzdak PD. A pharmacological characterization of the mGluR1 alpha subtype of the metabotropic glutamate receptor expressed in a cloned baby hamster kidney cell line. Brain Res. 1993 Aug 13;619(1-2):22–28. [PubMed]
  • de Ligt RA, Kourounakis AP, IJzerman AP. Inverse agonism at G protein-coupled receptors: (patho)physiological relevance and implications for drug discovery. Br J Pharmacol. 2000 May;130(1):1–12. [PMC free article] [PubMed]
  • Prézeau L, Gomeza J, Ahern S, Mary S, Galvez T, Bockaert J, Pin JP. Changes in the carboxyl-terminal domain of metabotropic glutamate receptor 1 by alternative splicing generate receptors with differing agonist-independent activity. Mol Pharmacol. 1996 Mar;49(3):422–429. [PubMed]
  • Ango F, Prézeau L, Muller T, Tu JC, Xiao B, Worley PF, Pin JP, Bockaert J, Fagni L. Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer. Nature. 2001 Jun 21;411(6840):962–965. [PubMed]
  • Kubokawa K, Miyashita T, Nagasawa H, Kubo Y. Cloning and characterization of a bifunctional metabotropic receptor activated by both extracellular calcium and glutamate. FEBS Lett. 1996 Aug 19;392(1):71–76. [PubMed]
  • Gabellini N, Manev RM, Candeo P, Favaron M, Manev H. Carboxyl domain of glutamate receptor directs its coupling to metabolic pathways. Neuroreport. 1993 May;4(5):531–534. [PubMed]
  • Kubo Y, Miyashita T, Murata Y. Structural basis for a Ca2+-sensing function of the metabotropic glutamate receptors. Science. 1998 Mar 13;279(5357):1722–1725. [PubMed]
  • Saunders R, Nahorski SR, Challiss RA. A modulatory effect of extracellular Ca2+ on type 1alpha metabotropic glutamate receptor-mediated signalling. Neuropharmacology. 1998;37(2):273–276. [PubMed]
  • Miyashita T, Kubo Y. Extracellular Ca2+ sensitivity of mGluR1alpha associated with persistent glutamate response in transfected CHO cells. Receptors Channels. 2000;7(1):25–40. [PubMed]
  • Cockcroft S, Thomas GM. Inositol-lipid-specific phospholipase C isoenzymes and their differential regulation by receptors. Biochem J. 1992 Nov 15;288(Pt 1):1–14. [PMC free article] [PubMed]
  • Eberhard DA, Holz RW. Intracellular Ca2+ activates phospholipase C. Trends Neurosci. 1988 Dec;11(12):517–520. [PubMed]
  • Wise A, Green A, Main MJ, Wilson R, Fraser N, Marshall FH. Calcium sensing properties of the GABA(B) receptor. Neuropharmacology. 1999 Nov;38(11):1647–1656. [PubMed]
  • Galvez T, Urwyler S, Prézeau L, Mosbacher J, Joly C, Malitschek B, Heid J, Brabet I, Froestl W, Bettler B, et al. Ca(2+) requirement for high-affinity gamma-aminobutyric acid (GABA) binding at GABA(B) receptors: involvement of serine 269 of the GABA(B)R1 subunit. Mol Pharmacol. 2000 Mar;57(3):419–426. [PubMed]
  • Nash MS, Saunders R, Young KW, Challiss RA, Nahorski SR. Reassessment of the Ca2+ sensing property of a type I metabotropic glutamate receptor by simultaneous measurement of inositol 1,4,5-trisphosphate and Ca2+ in single cells. J Biol Chem. 2001 Jun 1;276(22):19286–19293. [PubMed]
  • Baude A, Nusser Z, Molnár E, McIlhinney RA, Somogyi P. High-resolution immunogold localization of AMPA type glutamate receptor subunits at synaptic and non-synaptic sites in rat hippocampus. Neuroscience. 1995 Dec;69(4):1031–1055. [PubMed]
  • Petralia RS, Wang YX, Singh S, Wu C, Shi L, Wei J, Wenthold RJ. A monoclonal antibody shows discrete cellular and subcellular localizations of mGluR1 alpha metabotropic glutamate receptors. J Chem Neuroanat. 1997 Jul;13(2):77–93. [PubMed]
  • Alaluf S, Mulvihill ER, McIlhinney RA. Rapid agonist mediated phosphorylation of the metabotropic glutamate receptor 1 alpha by protein kinase C in permanently transfected BHK cells. FEBS Lett. 1995 Jul 3;367(3):301–305. [PubMed]
  • Hampson DR, Theriault E, Huang XP, Kristensen P, Pickering DS, Franck JE, Mulvihill ER. Characterization of two alternatively spliced forms of a metabotropic glutamate receptor in the central nervous system of the rat. Neuroscience. 1994 May;60(2):325–336. [PubMed]
  • Romano C, Yang WL, O'Malley KL. Metabotropic glutamate receptor 5 is a disulfide-linked dimer. J Biol Chem. 1996 Nov 8;271(45):28612–28616. [PubMed]
  • Robbins MJ, Ciruela F, Rhodes A, McIlhinney RA. Characterization of the dimerization of metabotropic glutamate receptors using an N-terminal truncation of mGluR1alpha. J Neurochem. 1999 Jun;72(6):2539–2547. [PubMed]
  • Fan GF, Ray K, Zhao XM, Goldsmith PK, Spiegel AM. Mutational analysis of the cysteines in the extracellular domain of the human Ca2+ receptor: effects on cell surface expression, dimerization and signal transduction. FEBS Lett. 1998 Oct 9;436(3):353–356. [PubMed]
  • Pace AJ, Gama L, Breitwieser GE. Dimerization of the calcium-sensing receptor occurs within the extracellular domain and is eliminated by Cys --> Ser mutations at Cys101 and Cys236. J Biol Chem. 1999 Apr 23;274(17):11629–11634. [PubMed]
  • Tsuji Y, Shimada Y, Takeshita T, Kajimura N, Nomura S, Sekiyama N, Otomo J, Usukura J, Nakanishi S, Jingami H. Cryptic dimer interface and domain organization of the extracellular region of metabotropic glutamate receptor subtype 1. J Biol Chem. 2000 Sep 8;275(36):28144–28151. [PubMed]
  • Romano C, Miller JK, Hyrc K, Dikranian S, Mennerick S, Takeuchi Y, Goldberg MP, O'Malley KL. Covalent and noncovalent interactions mediate metabotropic glutamate receptor mGlu5 dimerization. Mol Pharmacol. 2001 Jan;59(1):46–53. [PubMed]
  • Hébert TE, Bouvier M. Structural and functional aspects of G protein-coupled receptor oligomerization. Biochem Cell Biol. 1998;76(1):1–11. [PubMed]
  • Cvejic S, Devi LA. Dimerization of the delta opioid receptor: implication for a role in receptor internalization. J Biol Chem. 1997 Oct 24;272(43):26959–26964. [PubMed]
  • Jordan BA, Devi LA. G-protein-coupled receptor heterodimerization modulates receptor function. Nature. 1999 Jun 17;399(6737):697–700. [PMC free article] [PubMed]
  • Copani A, Romano C, Di Giorgi Gerevini V, Nicosia A, Casabona G, Storto M, Mutel V, Nicoletti F. Reducing conditions differentially affect the functional and structural properties of group-I and -II metabotropic glutamate receptors. Brain Res. 2000 Jun 9;867(1-2):165–172. [PubMed]
  • Ray K, Hauschild BC, Steinbach PJ, Goldsmith PK, Hauache O, Spiegel AM. Identification of the cysteine residues in the amino-terminal extracellular domain of the human Ca(2+) receptor critical for dimerization. Implications for function of monomeric Ca(2+) receptor. J Biol Chem. 1999 Sep 24;274(39):27642–27650. [PubMed]
  • Jones KA, Borowsky B, Tamm JA, Craig DA, Durkin MM, Dai M, Yao WJ, Johnson M, Gunwaldsen C, Huang LY, et al. GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2. Nature. 1998 Dec 17;396(6712):674–679. [PubMed]
  • Kaupmann K, Malitschek B, Schuler V, Heid J, Froestl W, Beck P, Mosbacher J, Bischoff S, Kulik A, Shigemoto R, et al. GABA(B)-receptor subtypes assemble into functional heteromeric complexes. Nature. 1998 Dec 17;396(6712):683–687. [PubMed]
  • White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, Barnes AA, Emson P, Foord SM, Marshall FH. Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature. 1998 Dec 17;396(6712):679–682. [PubMed]
  • Ciruela F, Escriche M, Burgueno J, Angulo E, Casado V, Soloviev MM, Canela EI, Mallol J, Chan WY, Lluis C, et al. Metabotropic glutamate 1alpha and adenosine A1 receptors assemble into functionally interacting complexes. J Biol Chem. 2001 May 25;276(21):18345–18351. [PubMed]
  • Mody N, Hermans E, Nahorski SR, Challiss RA. Inhibition of N-linked glycosylation of the human type 1alpha metabotropic glutamate receptor by tunicamycin: effects on cell-surface receptor expression and function. Neuropharmacology. 1999 Oct;38(10):1485–1492. [PubMed]
  • Hermans E, Young KW, Challiss RA, Nahorski SR. Effects of human type 1alpha metabotropic glutamate receptor expression level on phosphoinositide and Ca2+ signalling in an inducible cell expression system. J Neurochem. 1998 Apr;70(4):1772–1775. [PubMed]
  • Hermans E, Challiss RA, Nahorski SR. Effects of varying the expression level of recombinant human mGlu1alpha receptors on the pharmacological properties of agonists and antagonists. Br J Pharmacol. 1999 Feb;126(4):873–882. [PMC free article] [PubMed]
  • Aramori I, Nakanishi S. Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells. Neuron. 1992 Apr;8(4):757–765. [PubMed]
  • Thomsen C. Metabotropic glutamate receptor subtype 1A activates adenylate cyclase when expressed in baby hamster kidney cells. Prog Neuropsychopharmacol Biol Psychiatry. 1996 May;20(4):709–726. [PubMed]
  • Hermans E, Saunders R, Selkirk JV, Mistry R, Nahorski SR, Challiss RA. Complex involvement of pertussis toxin-sensitive G proteins in the regulation of type 1alpha metabotropic glutamate receptor signaling in baby hamster kidney cells. Mol Pharmacol. 2000 Aug;58(2):352–360. [PubMed]
  • Francesconi A, Duvoisin RM. Role of the second and third intracellular loops of metabotropic glutamate receptors in mediating dual signal transduction activation. J Biol Chem. 1998 Mar 6;273(10):5615–5624. [PubMed]
  • Parmentier ML, Joly C, Restituito S, Bockaert J, Grau Y, Pin JP. The G protein-coupling profile of metabotropic glutamate receptors, as determined with exogenous G proteins, is independent of their ligand recognition domain. Mol Pharmacol. 1998 Apr;53(4):778–786. [PubMed]
  • 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 Aug 8;272(32):20291–20298. [PubMed]
  • Hiltscher R, Seuwen K, Boddeke HW, Sommer B, Laurie DJ. Functional coupling of human metabotropic glutamate receptor hmGlu1d: comparison to splice variants hmGlu1a and -1b. Neuropharmacology. 1998 Jul;37(7):827–837. [PubMed]
  • Joly C, Gomeza J, Brabet I, Curry K, Bockaert J, Pin JP. Molecular, functional, and pharmacological characterization of the metabotropic glutamate receptor type 5 splice variants: comparison with mGluR1. J Neurosci. 1995 May;15(5 Pt 2):3970–3981. [PubMed]
  • Mary S, Stephan D, Gomeza J, Bockaert J, Pruss RM, Pin JP. The rat mGlu1d receptor splice variant shares functional properties with the other short isoforms of mGlu1 receptor. Eur J Pharmacol. 1997 Sep 17;335(1):65–72. [PubMed]
  • 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 Jul 5;267(19):13361–13368. [PubMed]
  • Balázs R, Miller S, Romano C, de Vries A, Chun Y, Cotman CW. Metabotropic glutamate receptor mGluR5 in astrocytes: pharmacological properties and agonist regulation. J Neurochem. 1997 Jul;69(1):151–163. [PubMed]
  • Kasahara J, Sugiyama H. Inositol phospholipid metabolism in Xenopus oocytes mediated by endogenous G(o) and Gi proteins. FEBS Lett. 1994 Nov 21;355(1):41–44. [PubMed]
  • Pickering DS, Thomsen C, Suzdak PD, Fletcher EJ, Robitaille R, Salter MW, MacDonald JF, Huang XP, Hampson DR. A comparison of two alternatively spliced forms of a metabotropic glutamate receptor coupled to phosphoinositide turnover. J Neurochem. 1993 Jul;61(1):85–92. [PubMed]
  • Selkirk JV, Price GW, Nahorski SR, Challiss RA. Cell type-specific differences in the coupling of recombinant mGlu1alpha receptors to endogenous G protein sub-populations. Neuropharmacology. 2001 Apr;40(5):645–656. [PubMed]
  • Pin JP, Waeber C, Prezeau L, Bockaert J, Heinemann SF. Alternative splicing generates metabotropic glutamate receptors inducing different patterns of calcium release in Xenopus oocytes. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10331–10335. [PMC free article] [PubMed]
  • Carruthers AM, Challiss RA, Mistry R, Saunders R, Thomsen C, Nahorski SR. Enhanced type 1alpha metabotropic glutamate receptor-stimulated phosphoinositide signaling after pertussis toxin treatment. Mol Pharmacol. 1997 Sep;52(3):406–414. [PubMed]
  • Akam EC, Carruthers AM, Nahorski SR, Challiss RA. Pharmacological characterization of type 1alpha metabotropic glutamate receptor-stimulated [35S]-GTPgammaS binding. Br J Pharmacol. 1997 Jul;121(6):1203–1209. [PMC free article] [PubMed]
  • Kammermeier PJ, Ikeda SR. Expression of RGS2 alters the coupling of metabotropic glutamate receptor 1a to M-type K+ and N-type Ca2+ channels. Neuron. 1999 Apr;22(4):819–829. [PubMed]
  • McCool BA, Pin JP, Harpold MM, Brust PF, Stauderman KA, Lovinger DM. Rat group I metabotropic glutamate receptors inhibit neuronal Ca2+ channels via multiple signal transduction pathways in HEK 293 cells. J Neurophysiol. 1998 Jan;79(1):379–391. [PubMed]
  • Ferraguti F, Baldani-Guerra B, Corsi M, Nakanishi S, Corti C. Activation of the extracellular signal-regulated kinase 2 by metabotropic glutamate receptors. Eur J Neurosci. 1999 Jun;11(6):2073–2082. [PubMed]
  • Choi S, Lovinger DM. Metabotropic glutamate receptor modulation of voltage-gated Ca2+ channels involves multiple receptor subtypes in cortical neurons. J Neurosci. 1996 Jan;16(1):36–45. [PubMed]
  • Sharon D, Vorobiov D, Dascal N. Positive and negative coupling of the metabotropic glutamate receptors to a G protein-activated K+ channel, GIRK, in Xenopus oocytes. J Gen Physiol. 1997 Apr;109(4):477–490. [PMC free article] [PubMed]
  • Hepler JR. Emerging roles for RGS proteins in cell signalling. Trends Pharmacol Sci. 1999 Sep;20(9):376–382. [PubMed]
  • Zhong H, Neubig RR. Regulator of G protein signaling proteins: novel multifunctional drug targets. J Pharmacol Exp Ther. 2001 Jun;297(3):837–845. [PubMed]
  • Gold SJ, Ni YG, Dohlman HG, Nestler EJ. Regulators of G-protein signaling (RGS) proteins: region-specific expression of nine subtypes in rat brain. J Neurosci. 1997 Oct 15;17(20):8024–8037. [PubMed]
  • Saugstad JA, Marino MJ, Folk JA, Hepler JR, Conn PJ. RGS4 inhibits signaling by group I metabotropic glutamate receptors. J Neurosci. 1998 Feb 1;18(3):905–913. [PubMed]
  • Boss V, Conn PJ. Metabotropic excitatory amino acid receptor activation stimulates phospholipase D in hippocampal slices. J Neurochem. 1992 Dec;59(6):2340–2343. [PubMed]
  • Pellegrini-Giampietro DE, Torregrossa SA, Moroni F. Pharmacological characterization of metabotropic glutamate receptors coupled to phospholipase D in the rat hippocampus. Br J Pharmacol. 1996 Jun;118(4):1035–1043. [PMC free article] [PubMed]
  • Klein J, Reymann KG, Riedel G. Activation of phospholipases C and D by the novel metabotropic glutamate receptor agonist tADA. Neuropharmacology. 1997 Feb;36(2):261–263. [PubMed]
  • Servitja JM, Masgrau R, Sarri E, Picatoste F. Group I metabotropic glutamate receptors mediate phospholipase D stimulation in rat cultured astrocytes. J Neurochem. 1999 Apr;72(4):1441–1447. [PubMed]
  • Shinomura T, del Río E, Breen KC, Downes CP, McLaughlin M. Activation of phospholipase D by metabotropic glutamate receptor agonists in rat cerebrocortical synaptosomes. Br J Pharmacol. 2000 Nov;131(5):1011–1018. [PMC free article] [PubMed]
  • Albani-Torregrossa S, Attucci S, Marinozzi M, Pellicciari R, Moroni F, Pellegrini-Giampietro DE. Antagonist pharmacology of metabotropic glutamate receptors coupled to phospholipase D activation in adult rat hippocampus: focus on (2R,1'S,2'R,3'S)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine versus 3, 5-dihydroxyphenylglycine. Mol Pharmacol. 1999 Apr;55(4):699–707. [PubMed]
  • Chavis P, Fagni L, Lansman JB, Bockaert J. Functional coupling between ryanodine receptors and L-type calcium channels in neurons. Nature. 1996 Aug 22;382(6593):719–722. [PubMed]
  • Fagni L, Chavis P, Ango F, Bockaert J. Complex interactions between mGluRs, intracellular Ca2+ stores and ion channels in neurons. Trends Neurosci. 2000 Feb;23(2):80–88. [PubMed]
  • Pollock J, Crawford JH, Wootton JF, Seabrook GR, Scott RH. Metabotropic glutamate receptor activation and intracellular cyclic ADP-ribose release Ca2+ from the same store in cultured DRG neurones. Cell Calcium. 1999 Sep-Oct;26(3-4):139–148. [PubMed]
  • del Río E, McLaughlin M, Downes CP, Nicholls DG. Differential coupling of G-protein-linked receptors to Ca2+ mobilization through inositol(1,4,5)trisphosphate or ryanodine receptors in cerebellar granule cells in primary culture. Eur J Neurosci. 1999 Sep;11(9):3015–3022. [PubMed]
  • Masgrau R, Servitja JM, Young KW, Pardo R, Sarri E, Nahorski SR, Picatoste F. Characterization of the metabotropic glutamate receptors mediating phospholipase C activation and calcium release in cerebellar granule cells: calcium-dependence of the phospholipase C response. Eur J Neurosci. 2001 Jan;13(2):248–256. [PubMed]
  • Rodríguez-Moreno A, Sistiaga A, Lerma J, Sánchez-Prieto J. Switch from facilitation to inhibition of excitatory synaptic transmission by group I mGluR desensitization. Neuron. 1998 Dec;21(6):1477–1486. [PubMed]
  • Savarese TM, Fraser CM. In vitro mutagenesis and the search for structure-function relationships among G protein-coupled receptors. Biochem J. 1992 Apr 1;283(Pt 1):1–19. [PMC free article] [PubMed]
  • Mary S, Gomeza J, Prézeau L, Bockaert J, Pin JP. A cluster of basic residues in the carboxyl-terminal tail of the short metabotropic glutamate receptor 1 variants impairs their coupling to phospholipase C. J Biol Chem. 1998 Jan 2;273(1):425–432. [PubMed]
  • Gomeza J, Joly C, Kuhn R, Knöpfel T, Bockaert J, Pin JP. The second intracellular loop of metabotropic glutamate receptor 1 cooperates with the other intracellular domains to control coupling to G-proteins. J Biol Chem. 1996 Jan 26;271(4):2199–2205. [PubMed]
  • Pin JP, Joly C, Heinemann SF, Bockaert J. Domains involved in the specificity of G protein activation in phospholipase C-coupled metabotropic glutamate receptors. EMBO J. 1994 Jan 15;13(2):342–348. [PMC free article] [PubMed]
  • Pin JP, Gomeza J, Joly C, Bockaert J. The metabotropic glutamate receptors: their second intracellular loop plays a critical role in the G-protein coupling specificity. Biochem Soc Trans. 1995 Feb;23(1):91–96. [PubMed]
  • Pin JP, Duvoisin R. The metabotropic glutamate receptors: structure and functions. Neuropharmacology. 1995 Jan;34(1):1–26. [PubMed]
  • Nitsch RM, Deng A, Wurtman RJ, Growdon JH. Metabotropic glutamate receptor subtype mGluR1alpha stimulates the secretion of the amyloid beta-protein precursor ectodomain. J Neurochem. 1997 Aug;69(2):704–712. [PubMed]
  • Chan WY, Soloviev MM, Ciruela F, McIlhinney RA. Molecular determinants of metabotropic glutamate receptor 1B trafficking. Mol Cell Neurosci. 2001 Mar;17(3):577–588. [PubMed]
  • Minakami R, Iida K, Hirakawa N, Sugiyama H. The expression of two splice variants of metabotropic glutamate receptor subtype 5 in the rat brain and neuronal cells during development. J Neurochem. 1995 Oct;65(4):1536–1542. [PubMed]
  • Mion S, Corti C, Neki A, Shigemoto R, Corsi M, Fumagalli G, Ferraguti F. Bidirectional regulation of neurite elaboration by alternatively spliced metabotropic glutamate receptor 5 (mGluR5) isoforms. Mol Cell Neurosci. 2001 Jun;17(6):957–972. [PubMed]
  • Hall RA, Premont RT, Lefkowitz RJ. Heptahelical receptor signaling: beyond the G protein paradigm. J Cell Biol. 1999 May 31;145(5):927–932. [PMC free article] [PubMed]
  • Heuss C, Gerber U. G-protein-independent signaling by G-protein-coupled receptors. Trends Neurosci. 2000 Oct;23(10):469–475. [PubMed]
  • Heuss C, Scanziani M, Gähwiler BH, Gerber U. G-protein-independent signaling mediated by metabotropic glutamate receptors. Nat Neurosci. 1999 Dec;2(12):1070–1077. [PubMed]
  • Cao W, Luttrell LM, Medvedev AV, Pierce KL, Daniel KW, Dixon TM, Lefkowitz RJ, Collins S. Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activation. J Biol Chem. 2000 Dec 8;275(49):38131–38134. [PubMed]
  • Lefkowitz RJ. G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization. J Biol Chem. 1998 Jul 24;273(30):18677–18680. [PubMed]
  • Luttrell LM, Ferguson SS, Daaka Y, Miller WE, Maudsley S, Della Rocca GJ, Lin F, Kawakatsu H, Owada K, Luttrell DK, et al. Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. Science. 1999 Jan 29;283(5402):655–661. [PubMed]
  • DeFea KA, Zalevsky J, Thoma MS, Déry O, Mullins RD, Bunnett NW. beta-arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2. J Cell Biol. 2000 Mar 20;148(6):1267–1281. [PMC free article] [PubMed]
  • Peavy RD, Conn PJ. Phosphorylation of mitogen-activated protein kinase in cultured rat cortical glia by stimulation of metabotropic glutamate receptors. J Neurochem. 1998 Aug;71(2):603–612. [PubMed]
  • Schinkmann KA, Kim TA, Avraham S. Glutamate-stimulated activation of DNA synthesis via mitogen-activated protein kinase in primary astrocytes: involvement of protein kinase C and related adhesion focal tyrosine kinase. J Neurochem. 2000 May;74(5):1931–1940. [PubMed]
  • Karim F, Wang CC, Gereau RW., 4th Metabotropic glutamate receptor subtypes 1 and 5 are activators of extracellular signal-regulated kinase signaling required for inflammatory pain in mice. J Neurosci. 2001 Jun 1;21(11):3771–3779. [PubMed]
  • Mundell SJ, Matharu AL, Pula G, Roberts PJ, Kelly E. Agonist-induced internalization of the metabotropic glutamate receptor 1a is arrestin- and dynamin-dependent. J Neurochem. 2001 Aug;78(3):546–551. [PubMed]
  • Doherty AJ, Coutinho V, Collingridge GL, Henley JM. Rapid internalization and surface expression of a functional, fluorescently tagged G-protein-coupled glutamate receptor. Biochem J. 1999 Jul 15;341(Pt 2):415–422. [PMC free article] [PubMed]
  • Scannevin RH, Huganir RL. Postsynaptic organization and regulation of excitatory synapses. Nat Rev Neurosci. 2000 Nov;1(2):133–141. [PubMed]
  • Pak Y, Kouvelas A, Scheideler MA, Rasmussen J, O'Dowd BF, George SR. Agonist-induced functional desensitization of the mu-opioid receptor is mediated by loss of membrane receptors rather than uncoupling from G protein. Mol Pharmacol. 1996 Nov;50(5):1214–1222. [PubMed]
  • 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 Apr 6;494(1-2):60–63. [PubMed]
  • Kim E, Cho KO, Rothschild A, Sheng M. Heteromultimerization and NMDA receptor-clustering activity of Chapsyn-110, a member of the PSD-95 family of proteins. Neuron. 1996 Jul;17(1):103–113. [PubMed]
  • van Rossum D, Hanisch UK. Cytoskeletal dynamics in dendritic spines: direct modulation by glutamate receptors? Trends Neurosci. 1999 Jul;22(7):290–295. [PubMed]
  • Dong H, O'Brien RJ, Fung ET, Lanahan AA, Worley PF, Huganir RL. GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors. Nature. 1997 Mar 20;386(6622):279–284. [PubMed]
  • Garcia EP, Mehta S, Blair LA, Wells DG, Shang J, Fukushima T, Fallon JR, Garner CC, Marshall J. SAP90 binds and clusters kainate receptors causing incomplete desensitization. Neuron. 1998 Oct;21(4):727–739. [PubMed]
  • Lujan R, Nusser Z, Roberts JD, Shigemoto R, Somogyi P. Perisynaptic location of metabotropic glutamate receptors mGluR1 and mGluR5 on dendrites and dendritic spines in the rat hippocampus. Eur J Neurosci. 1996 Jul;8(7):1488–1500. [PubMed]
  • Brakeman PR, Lanahan AA, O'Brien R, Roche K, Barnes CA, Huganir RL, Worley PF. Homer: a protein that selectively binds metabotropic glutamate receptors. Nature. 1997 Mar 20;386(6622):284–288. [PubMed]
  • Kato A, Ozawa F, Saitoh Y, Fukazawa Y, Sugiyama H, Inokuchi K. Novel members of the Vesl/Homer family of PDZ proteins that bind metabotropic glutamate receptors. J Biol Chem. 1998 Sep 11;273(37):23969–23975. [PubMed]
  • Soloviev MM, Ciruela F, Chan WY, McIlhinney RA. Molecular characterisation of two structurally distinct groups of human homers, generated by extensive alternative splicing. J Mol Biol. 2000 Feb 4;295(5):1185–1200. [PubMed]
  • Tu JC, Xiao B, Yuan JP, Lanahan AA, Leoffert K, Li M, Linden DJ, Worley PF. Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors. Neuron. 1998 Oct;21(4):717–726. [PubMed]
  • Xiao B, Tu JC, Petralia RS, Yuan JP, Doan A, Breder CD, Ruggiero A, Lanahan AA, Wenthold RJ, Worley PF. Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins. Neuron. 1998 Oct;21(4):707–716. [PubMed]
  • Tadokoro S, Tachibana T, Imanaka T, Nishida W, Sobue K. Involvement of unique leucine-zipper motif of PSD-Zip45 (Homer 1c/vesl-1L) in group 1 metabotropic glutamate receptor clustering. Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13801–13806. [PMC free article] [PubMed]
  • Ciruela F, Soloviev MM, McIlhinney RA. Co-expression of metabotropic glutamate receptor type 1alpha with homer-1a/Vesl-1S increases the cell surface expression of the receptor. Biochem J. 1999 Aug 1;341(Pt 3):795–803. [PMC free article] [PubMed]
  • Roche KW, Tu JC, Petralia RS, Xiao B, Wenthold RJ, Worley PF. Homer 1b regulates the trafficking of group I metabotropic glutamate receptors. J Biol Chem. 1999 Sep 3;274(36):25953–25957. [PubMed]
  • 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 Jan;15(1):36–50. [PubMed]
  • Ango F, Pin JP, Tu JC, Xiao B, Worley PF, Bockaert J, Fagni L. Dendritic and axonal targeting of type 5 metabotropic glutamate receptor is regulated by homer1 proteins and neuronal excitation. J Neurosci. 2000 Dec 1;20(23):8710–8716. [PubMed]
  • Naisbitt S, Kim E, Tu JC, Xiao B, Sala C, Valtschanoff J, Weinberg RJ, Worley PF, Sheng M. Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron. 1999 Jul;23(3):569–582. [PubMed]
  • Tu JC, Xiao B, Naisbitt S, Yuan JP, Petralia RS, Brakeman P, Doan A, Aakalu VK, Lanahan AA, Sheng M, et al. Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. Neuron. 1999 Jul;23(3):583–592. [PubMed]
  • Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SG. Proteomic analysis of NMDA receptor-adhesion protein signaling complexes. Nat Neurosci. 2000 Jul;3(7):661–669. [PubMed]
  • Kammermeier PJ, Xiao B, Tu JC, Worley PF, Ikeda SR. Homer proteins regulate coupling of group I metabotropic glutamate receptors to N-type calcium and M-type potassium channels. J Neurosci. 2000 Oct 1;20(19):7238–7245. [PubMed]
  • Foa L, Rajan I, Haas K, Wu GY, Brakeman P, Worley P, Cline H. The scaffold protein, Homer1b/c, regulates axon pathfinding in the central nervous system in vivo. Nat Neurosci. 2001 May;4(5):499–506. [PubMed]
  • Sheng M. Excitatory synapses. Glutamate receptors put in their place. Nature. 1997 Mar 20;386(6622):221–223. [PubMed]
  • Krupnick JG, Benovic JL. The role of receptor kinases and arrestins in G protein-coupled receptor regulation. Annu Rev Pharmacol Toxicol. 1998;38:289–319. [PubMed]
  • Ferguson SS. Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol Rev. 2001 Mar;53(1):1–24. [PubMed]
  • Catania MV, Aronica E, Sortino MA, Canonico PL, Nicoletti F. Desensitization of metabotropic glutamate receptors in neuronal cultures. J Neurochem. 1991 Apr;56(4):1329–1335. [PubMed]
  • Aronica E, Dell'Albani P, Condorelli DF, Nicoletti F, Hack N, Balázs R. Mechanisms underlying developmental changes in the expression of metabotropic glutamate receptors in cultured cerebellar granule cells: homologous desensitization and interactive effects involving N-methyl-D-aspartate receptors. Mol Pharmacol. 1993 Nov;44(5):981–989. [PubMed]
  • Lonart G, Alagarsamy S, Ravula R, Wang J, Johnson KM. Inhibition of the phospholipase C-linked metabotropic glutamate receptor by 2-amino-3-phosphonopropionate is dependent on extracellular calcium. J Neurochem. 1992 Aug;59(2):772–775. [PubMed]
  • Canonico PL, Favit A, Catania MV, Nicoletti F. Phorbol esters attenuate glutamate-stimulated inositol phospholipid hydrolysis in neuronal cultures. J Neurochem. 1988 Oct;51(4):1049–1053. [PubMed]
  • Gereau RW, 4th, Heinemann SF. Role of protein kinase C phosphorylation in rapid desensitization of metabotropic glutamate receptor 5. Neuron. 1998 Jan;20(1):143–151. [PubMed]
  • Kawabata S, Tsutsumi R, Kohara A, Yamaguchi T, Nakanishi S, Okada M. Control of calcium oscillations by phosphorylation of metabotropic glutamate receptors. Nature. 1996 Sep 5;383(6595):89–92. [PubMed]
  • Nakahara K, Okada M, Nakanishi S. The metabotropic glutamate receptor mGluR5 induces calcium oscillations in cultured astrocytes via protein kinase C phosphorylation. J Neurochem. 1997 Oct;69(4):1467–1475. [PubMed]
  • Flint AC, Dammerman RS, Kriegstein AR. Endogenous activation of metabotropic glutamate receptors in neocortical development causes neuronal calcium oscillations. Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):12144–12149. [PMC free article] [PubMed]
  • Codazzi F, Teruel MN, Meyer T. Control of astrocyte Ca(2+) oscillations and waves by oscillating translocation and activation of protein kinase C. Curr Biol. 2001 Jul 24;11(14):1089–1097. [PubMed]
  • Kawabata S, Kohara A, Tsutsumi R, Itahana H, Hayashibe S, Yamaguchi T, Okada M. Diversity of calcium signaling by metabotropic glutamate receptors. J Biol Chem. 1998 Jul 10;273(28):17381–17385. [PubMed]
  • Dale LB, Babwah AV, Bhattacharya M, Kelvin DJ, Ferguson SS. Spatial-temporal patterning of metabotropic glutamate receptor-mediated inositol 1,4,5-triphosphate, calcium, and protein kinase C oscillations: protein kinase C-dependent receptor phosphorylation is not required. J Biol Chem. 2001 Sep 21;276(38):35900–35908. [PubMed]
  • Dolmetsch RE, Xu K, Lewis RS. Calcium oscillations increase the efficiency and specificity of gene expression. Nature. 1998 Apr 30;392(6679):933–936. [PubMed]
  • Li W, Llopis J, Whitney M, Zlokarnik G, Tsien RY. Cell-permeant caged InsP3 ester shows that Ca2+ spike frequency can optimize gene expression. Nature. 1998 Apr 30;392(6679):936–941. [PubMed]
  • Hu Q, Deshpande S, Irani K, Ziegelstein RC. [Ca(2+)](i) oscillation frequency regulates agonist-stimulated NF-kappaB transcriptional activity. J Biol Chem. 1999 Nov 26;274(48):33995–33998. [PubMed]
  • Hardingham GE, Arnold FJ, Bading H. Nuclear calcium signaling controls CREB-mediated gene expression triggered by synaptic activity. Nat Neurosci. 2001 Mar;4(3):261–267. [PubMed]
  • Wang D, Sadée W, Quillan JM. Calmodulin binding to G protein-coupling domain of opioid receptors. J Biol Chem. 1999 Jul 30;274(31):22081–22088. [PubMed]
  • Bofill-Cardona E, Kudlacek O, Yang Q, Ahorn H, Freissmuth M, Nanoff C. Binding of calmodulin to the D2-dopamine receptor reduces receptor signaling by arresting the G protein activation switch. J Biol Chem. 2000 Oct 20;275(42):32672–32680. [PubMed]
  • Alagarsamy S, Marino MJ, Rouse ST, Gereau RW, 4th, Heinemann SF, Conn PJ. Activation of NMDA receptors reverses desensitization of mGluR5 in native and recombinant systems. Nat Neurosci. 1999 Mar;2(3):234–240. [PubMed]
  • Francesconi A, Duvoisin RM. Opposing effects of protein kinase C and protein kinase A on metabotropic glutamate receptor signaling: selective desensitization of the inositol trisphosphate/Ca2+ pathway by phosphorylation of the receptor-G protein-coupling domain. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6185–6190. [PMC free article] [PubMed]
  • Herrero I, Miras-Portugal MT, Sánchez-Prieto J. Rapid desensitization of the metabotropic glutamate receptor that facilitates glutamate release in rat cerebrocortical nerve terminals. Eur J Neurosci. 1994 Jan 1;6(1):115–120. [PubMed]
  • Fiorillo CD, Williams JT. Glutamate mediates an inhibitory postsynaptic potential in dopamine neurons. Nature. 1998 Jul 2;394(6688):78–82. [PubMed]
  • Ciruela F, Giacometti A, McIlhinney RA. Functional regulation of metabotropic glutamate receptor type 1c: a role for phosphorylation in the desensitization of the receptor. FEBS Lett. 1999 Dec 3;462(3):278–282. [PubMed]
  • Dale LB, Bhattacharya M, Anborgh PH, Murdoch B, Bhatia M, Nakanishi S, Ferguson SS. G protein-coupled receptor kinase-mediated desensitization of metabotropic glutamate receptor 1A protects against cell death. J Biol Chem. 2000 Dec 8;275(49):38213–38220. [PubMed]
  • Sallese M, Salvatore L, D'Urbano E, Sala G, Storto M, Launey T, Nicoletti F, Knöpfel T, De Blasi A. The G-protein-coupled receptor kinase GRK4 mediates homologous desensitization of metabotropic glutamate receptor 1. FASEB J. 2000 Dec;14(15):2569–2580. [PubMed]
  • Ciruela F, McIlhinney RA. Differential internalisation of mGluR1 splice variants in response to agonist and phorbol esters in permanently transfected BHK cells. FEBS Lett. 1997 Nov 24;418(1-2):83–86. [PubMed]
  • Spooren WP, Gasparini F, Salt TE, Kuhn R. Novel allosteric antagonists shed light on mglu(5) receptors and CNS disorders. Trends Pharmacol Sci. 2001 Jul;22(7):331–337. [PubMed]
  • Sato M, Suzuki K, Nakanishi S. NMDA receptor stimulation and brain-derived neurotrophic factor upregulate homer 1a mRNA via the mitogen-activated protein kinase cascade in cultured cerebellar granule cells. J Neurosci. 2001 Jun 1;21(11):3797–3805. [PubMed]
  • Hubert GW, Paquet M, Smith Y. Differential subcellular localization of mGluR1a and mGluR5 in the rat and monkey Substantia nigra. J Neurosci. 2001 Mar 15;21(6):1838–1847. [PubMed]
  • Nakamura T, Barbara JG, Nakamura K, Ross WN. Synergistic release of Ca2+ from IP3-sensitive stores evoked by synaptic activation of mGluRs paired with backpropagating action potentials. Neuron. 1999 Nov;24(3):727–737. [PubMed]
  • Rae MG, Martin DJ, Collingridge GL, Irving AJ. Role of Ca2+ stores in metabotropic L-glutamate receptor-mediated supralinear Ca2+ signaling in rat hippocampal neurons. J Neurosci. 2000 Dec 1;20(23):8628–8636. [PubMed]
  • Emptage NJ. Calcium on the up: supralinear calcium signaling in central neurons. Neuron. 1999 Nov;24(3):495–497. [PubMed]
  • Umemori H, Inoue T, Kume S, Sekiyama N, Nagao M, Itoh H, Nakanishi S, Mikoshiba K, Yamamoto T. Activation of the G protein Gq/11 through tyrosine phosphorylation of the alpha subunit. Science. 1997 Jun 20;276(5320):1878–1881. [PubMed]
  • Tozzi A, Guatteo E, Caputi L, Bernardi G, Mercuri NB. Group I mGluRs coupled to G proteins are regulated by tyrosine kinase in dopamine neurons of the rat midbrain. J Neurophysiol. 2001 Jun;85(6):2490–2497. [PubMed]
  • Canossa M, Gärtner A, Campana G, Inagaki N, Thoenen H. Regulated secretion of neurotrophins by metabotropic glutamate group I (mGluRI) and Trk receptor activation is mediated via phospholipase C signalling pathways. EMBO J. 2001 Apr 2;20(7):1640–1650. [PMC free article] [PubMed]
  • Zhu H, Ryan K, Chen S. Cloning of novel splice variants of mouse mGluR1. Brain Res Mol Brain Res. 1999 Nov 10;73(1-2):93–103. [PubMed]
  • Soloviev MM, Ciruela F, Chan WY, McIlhinney RA. Identification, cloning and analysis of expression of a new alternatively spliced form of the metabotropic glutamate receptor mGluR1 mRNA1. Biochim Biophys Acta. 1999 Jul 7;1446(1-2):161–166. [PubMed]
  • Makoff AJ, Phillips T, Pilling C, Emson P. Expression of a novel splice variant of human mGluR1 in the cerebellum. Neuroreport. 1997 Sep 8;8(13):2943–2947. [PubMed]
  • Ray K, Hauschild BC. Cys-140 is critical for metabotropic glutamate receptor-1 dimerization. J Biol Chem. 2000 Nov 3;275(44):34245–34251. [PubMed]
  • Seal AJ, Collingridge GL, Henley JM. In vitro translation and membrane topology of rat recombinant mGluR1 alpha. Neuropharmacology. 1994 Sep;33(9):1065–1070. [PubMed]
  • Alaluf S, Mulvihill ER, McIlhinney RA. Palmitoylation of metabotropic glutamate receptor subtype 4 but not 1 alpha expressed in permanently transfected BHK cells. Biochem Soc Trans. 1995 Feb;23(1):87S–87S. [PubMed]
  • Desai MA, Burnett JP, Mayne NG, Schoepp DD. Cloning and expression of a human metabotropic glutamate receptor 1 alpha: enhanced coupling on co-transfection with a glutamate transporter. Mol Pharmacol. 1995 Oct;48(4):648–657. [PubMed]
  • Tanabe Y, Masu M, Ishii T, Shigemoto R, Nakanishi S. A family of metabotropic glutamate receptors. Neuron. 1992 Jan;8(1):169–179. [PubMed]
  • Minakami R, Katsuki F, Yamamoto T, Nakamura K, Sugiyama H. Molecular cloning and the functional expression of two isoforms of human metabotropic glutamate receptor subtype 5. Biochem Biophys Res Commun. 1994 Mar 30;199(3):1136–1143. [PubMed]
  • Daggett LP, Sacaan AI, Akong M, Rao SP, Hess SD, Liaw C, Urrutia A, Jachec C, Ellis SB, Dreessen J, et al. Molecular and functional characterization of recombinant human metabotropic glutamate receptor subtype 5. Neuropharmacology. 1995 Aug;34(8):871–886. [PubMed]
  • Minakami R, Katsuki F, Sugiyama H. A variant of metabotropic glutamate receptor subtype 5: an evolutionally conserved insertion with no termination codon. Biochem Biophys Res Commun. 1993 Jul 30;194(2):622–627. [PubMed]
  • Flor PJ, Lindauer K, Püttner I, Rüegg D, Lukic S, Knöpfel T, Kuhn R. Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 2. Eur J Neurosci. 1995 Apr 1;7(4):622–629. [PubMed]
  • Makoff A, Volpe F, Lelchuk R, Harrington K, Emson P. Molecular characterization and localization of human metabotropic glutamate receptor type 3. Brain Res Mol Brain Res. 1996 Aug;40(1):55–63. [PubMed]
  • Wu S, Wright RA, Rockey PK, Burgett SG, Arnold JS, Rosteck PR, Jr, Johnson BG, Schoepp DD, Belagaje RM. Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells. Brain Res Mol Brain Res. 1998 Jan;53(1-2):88–97. [PubMed]
  • Thomsen C, Pekhletski R, Haldeman B, Gilbert TA, O'Hara P, Hampson DR. Cloning and characterization of a metabotropic glutamate receptor, mGluR4b. Neuropharmacology. 1997 Jan;36(1):21–30. [PubMed]
  • Hashimoto T, Inazawa J, Okamoto N, Tagawa Y, Bessho Y, Honda Y, Nakanishi S. The whole nucleotide sequence and chromosomal localization of the gene for human metabotropic glutamate receptor subtype 6. Eur J Neurosci. 1997 Jun;9(6):1226–1235. [PubMed]
  • Nakajima Y, Iwakabe H, Akazawa C, Nawa H, Shigemoto R, Mizuno N, Nakanishi S. 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 Jun 5;268(16):11868–11873. [PubMed]
  • Makoff A, Pilling C, Harrington K, Emson P. Human metabotropic glutamate receptor type 7: molecular cloning and mRNA distribution in the CNS. Brain Res Mol Brain Res. 1996 Aug;40(1):165–170. [PubMed]
  • Saugstad JA, Kinzie JM, Mulvihill ER, Segerson TP, Westbrook GL. Cloning and expression of a new member of the L-2-amino-4-phosphonobutyric acid-sensitive class of metabotropic glutamate receptors. Mol Pharmacol. 1994 Mar;45(3):367–372. [PubMed]
  • Okamoto N, Hori S, Akazawa C, Hayashi Y, Shigemoto R, Mizuno N, Nakanishi S. Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction. J Biol Chem. 1994 Jan 14;269(2):1231–1236. [PubMed]
  • Flor PJ, Van Der Putten H, Rüegg D, Lukic S, Leonhardt T, Bence M, Sansig G, Knöpfel T, Kuhn R. A novel splice variant of a metabotropic glutamate receptor, human mGluR7b. Neuropharmacology. 1997 Feb;36(2):153–159. [PubMed]
  • Corti C, Restituito S, Rimland JM, Brabet I, Corsi M, Pin JP, Ferraguti F. Cloning and characterization of alternative mRNA forms for the rat metabotropic glutamate receptors mGluR7 and mGluR8. Eur J Neurosci. 1998 Dec;10(12):3629–3641. [PubMed]
  • Saugstad JA, Kinzie JM, Shinohara MM, Segerson TP, Westbrook GL. Cloning and expression of rat metabotropic glutamate receptor 8 reveals a distinct pharmacological profile. Mol Pharmacol. 1997 Jan;51(1):119–125. [PubMed]
  • 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 Apr 20;67(2):201–210. [PubMed]
  • Corti C, Cavanni P, Caveggion E, Ferraguti F, Corsi M, Trist DG. Different levels of receptor expression as a new procedure to estimate agonist affinity constant. Application to the metabotropic receptors. Ann N Y Acad Sci. 1997 May 30;812:231–233. [PubMed]
  • Shiraishi Y, Mizutani A, Bito H, Fujisawa K, Narumiya S, Mikoshiba K, Furuichi T. Cupidin, an isoform of Homer/Vesl, interacts with the actin cytoskeleton and activated rho family small GTPases and is expressed in developing mouse cerebellar granule cells. J Neurosci. 1999 Oct 1;19(19):8389–8400. [PubMed]
  • 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 Jan;72(1):346–354. [PubMed]
  • Ciruela F, McIlhinney RA. Metabotropic glutamate receptor type 1alpha and tubulin assemble into dynamic interacting complexes. J Neurochem. 2001 Feb;76(3):750–757. [PubMed]
  • Luján R, Ciruela F. Immunocytochemical localization of metabotropic glutamate receptor type 1 alpha and tubulin in rat brain. Neuroreport. 2001 May 8;12(6):1285–1291. [PubMed]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • Gene
    Gene links
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene links
  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...