Group I Metabotropic Glutamate Receptors (mGluRs): Ins and Outs

  • Prabhat Kumar Mahato
  • Namrata Ramsakha
  • Prachi Ojha
  • Ravinder Gulia
  • Rohan Sharma
  • Samarjit BhattacharyyaEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1112)


Glutamate is a nonessential amino acid, known to act as a major excitatory neurotransmitter in the central nervous system. Glutamate transduces its signal by activating two types of receptors, viz., ionotropic glutamate receptors and metabotropic glutamate receptors (mGluRs). mGluR1 and mGluR5 are members of the group I mGluR family, and they belong to the G-protein-coupled receptor (GPCR) family. These receptors are involved in various forms of synaptic plasticity including learning and memory. Similar to many other GPCRs, trafficking plays a critical role in controlling the spatiotemporal localization of these receptors on the cell surface, which is critical for the normal ligand/receptor interaction. Improper targeting of GPCRs results in aberrant signaling, which often leads to various diseases. Trafficking also regulates the activity of these receptors. Thus, inappropriate trafficking of these receptors might have pathological consequences. Group I mGluRs have been implicated in various neuropsychiatric disorders like Fragile X syndrome, autism, etc. In this review, we discuss the current understanding of group I mGluR trafficking in the central nervous system and its physiological importance.


Endocytosis Trafficking Desensitization Receptor recycling GPCR Metabotropic glutamate receptors Neurotransmitter receptors 


  1. Abdul-Ghani MA, Valiante TA, Carlen PL, Pennefather PS (1996) Metabotropic glutamate receptors coupled to IP3 production mediate inhibition of IAHP in rat dentate granule neurons. J Neurophysiol 76:2691–2700CrossRefGoogle Scholar
  2. Adams CL, Cowen MS, Short JL, Lawrence AJ (2008) Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats. Int J Neuropsychopharmacol 11:229–241. CrossRefPubMedGoogle Scholar
  3. Aramori I, Nakanishi S (1992) Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells. Neuron 8:757–765CrossRefGoogle Scholar
  4. Barak LS, Tiberi M, Freedman NJ, Kwatra MM, Lefkowitz RJ, Caron MG (1994) A highly conserved tyrosine residue in G protein-coupled receptors is required for agonist-mediated beta 2-adrenergic receptor sequestration. J Biol Chem 269:2790–2795PubMedGoogle Scholar
  5. Bassell GJ, Warren ST (2008) Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function. Neuron 60:201–214. CrossRefPubMedPubMedCentralGoogle Scholar
  6. Baude A, Nusser Z, Roberts JD, Mulvihill E, McIlhinney RA, Somogyi P (1993) The metabotropic glutamate receptor (mGluR1 alpha) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron 11:771–787CrossRefGoogle Scholar
  7. Bear MF, Huber KM, Warren ST (2004) The mGluR theory of fragile X mental retardation. Trends Neurosci 27:370–377. CrossRefPubMedGoogle Scholar
  8. Besheer J, Grondin JJ, Cannady R, Sharko AC, Faccidomo S, Hodge CW (2010) Metabotropic glutamate receptor 5 activity in the nucleus accumbens is required for the maintenance of ethanol self-administration in a rat genetic model of high alcohol intake. Biol Psychiatry 67:812–822. CrossRefPubMedGoogle Scholar
  9. Bhatnagar A, Willins DL, Gray JA, Woods J, Benovic JL, Roth BL (2001) The dynamin-dependent, arrestin-independent internalization of 5-hydroxytryptamine 2A (5-HT2A) serotonin receptors reveals differential sorting of arrestins and 5-HT2A receptors during endocytosis. J Biol Chem 276:8269–8277. CrossRefPubMedGoogle Scholar
  10. Bhattacharya M, Babwah AV, Godin C, Anborgh PH, Dale LB, Poulter MO, Ferguson SS (2004) Ral and phospholipase D2-dependent pathway for constitutive metabotropic glutamate receptor endocytosis. J Neurosci: Off J Soc Neurosci 24:8752–8761. CrossRefGoogle Scholar
  11. Bhattacharyya S (2016) Inside story of Group I Metabotropic Glutamate Receptors (mGluRs). Int J Biochem Cell Biol 77:205–212. CrossRefPubMedGoogle Scholar
  12. Bird MK, Kirchhoff J, Djouma E, Lawrence AJ (2008) Metabotropic glutamate 5 receptors regulate sensitivity to ethanol in mice. Int J Neuropsychopharmacol 11:765–774. CrossRefPubMedGoogle Scholar
  13. Black JB, Premont RT, Daaka Y (2016) Feedback regulation of G protein-coupled receptor signaling by GRKs and arrestins. Semin Cell Dev Biol 50:95–104. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Blednov YA, Harris RA (2008) Metabotropic glutamate receptor 5 (mGluR5) regulation of ethanol sedation, dependence and consumption: relationship to acamprosate actions. Int J Neuropsychopharmacol 11:775–793. CrossRefPubMedPubMedCentralGoogle Scholar
  15. Brown WT, Friedman E, Jenkins EC, Brooks J, Wisniewski K, Raguthu S, French JH (1982a) Association of fragile X syndrome with autism. Lancet 1:100CrossRefGoogle Scholar
  16. Brown WT, Jenkins EC, Friedman E, Brooks J, Wisniewski K, Raguthu S, French J (1982b) Autism is associated with the fragile-X syndrome. J Autism Dev Disord 12:303–308CrossRefGoogle Scholar
  17. Buxbaum JD, Oishi M, Chen HI, Pinkas-Kramarski R, Jaffe EA, Gandy SE, Greengard P (1992) Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer beta/A4 amyloid protein precursor. Proc Natl Acad Sci U S A 89:10075–10078CrossRefGoogle Scholar
  18. Caporaso GL, Gandy SE, Buxbaum JD, Ramabhadran TV, Greengard P (1992) Protein phosphorylation regulates secretion of Alzheimer beta/A4 amyloid precursor protein. Proc Natl Acad Sci U S A 89:3055–3059CrossRefGoogle Scholar
  19. Catania MV, Landwehrmeyer GB, Testa CM, Standaert DG, Penney JB Jr, Young AB (1994) Metabotropic glutamate receptors are differentially regulated during development. Neuroscience 61:481–495CrossRefGoogle Scholar
  20. Citri A, Malenka RC (2008) Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacol: Off Publ Am Coll Neuropsychopharmacol 33:18–41. CrossRefGoogle Scholar
  21. Claing A, Laporte SA, Caron MG, Lefkowitz RJ (2002) Endocytosis of G protein-coupled receptors: roles of G protein-coupled receptor kinases and beta-arrestin proteins. Progress in neurobiology 66:61–79CrossRefGoogle Scholar
  22. Conn PJ, Pin JP (1997) Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 37:205–237CrossRefGoogle Scholar
  23. Cozzoli DK et al (2012) Nucleus accumbens mGluR5-associated signaling regulates binge alcohol drinking under drinking-in-the-dark procedures. Alcohol Clin Exp Res 36:1623–1633. CrossRefPubMedPubMedCentralGoogle Scholar
  24. Cozzoli DK et al (2009) Binge drinking upregulates accumbens mGluR5-Homer2-PI3K signaling: functional implications for alcoholism. J Neurosci: Off J Soc Neurosci 29:8655–8668. CrossRefGoogle Scholar
  25. Dale LB, Bhattacharya M, Anborgh PH, Murdoch B, Bhatia M, Nakanishi S, Ferguson SS (2000) G protein-coupled receptor kinase-mediated desensitization of metabotropic glutamate receptor 1A protects against cell death. J Biol Chem 275:38213–38220CrossRefGoogle Scholar
  26. Dale LB, Bhattacharya M, Seachrist JL, Anborgh PH, Ferguson SS (2001) Agonist-stimulated and tonic internalization of metabotropic glutamate receptor 1a in human embryonic kidney 293 cells: agonist-stimulated endocytosis is beta-arrestin1 isoform-specific. Mol Pharmacol 60:1243–1253CrossRefGoogle Scholar
  27. Dhami GK, Anborgh PH, Dale LB, Sterne-Marr R, Ferguson SS (2002) Phosphorylation-independent regulation of metabotropic glutamate receptor signaling by G protein-coupled receptor kinase 2. J Biol Chem 277:25266–25272. CrossRefPubMedGoogle Scholar
  28. Dhami GK, Ferguson SS (2006) Regulation of metabotropic glutamate receptor signaling, desensitization and endocytosis. Pharmacol Ther 111:260–271CrossRefGoogle Scholar
  29. Dolen G, Osterweil E, Rao BS, Smith GB, Auerbach BD, Chattarji S, Bear MF (2007) Correction of fragile X syndrome in mice. Neuron 56:955–962CrossRefGoogle Scholar
  30. Drake MT, Shenoy SK, Lefkowitz RJ (2006) Trafficking of G protein-coupled receptors. Circ Res 99:570–582CrossRefGoogle Scholar
  31. Ferguson SS (2001) Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol Rev 53:1–24PubMedGoogle Scholar
  32. Ferguson SS, Barak LS, Zhang J, Caron MG (1996) G-protein-coupled receptor regulation: role of G-protein-coupled receptor kinases and arrestins. Can J Physiol Pharmacol 74:1095–1110CrossRefGoogle Scholar
  33. Fourgeaud L, Bessis AS, Rossignol F, Pin JP, Olivo-Marin JC, Hemar A (2003) The metabotropic glutamate receptor mGluR5 is endocytosed by a clathrin-independent pathway. J Biol Chem 278:12222–12230CrossRefGoogle Scholar
  34. Francesconi A, Duvoisin RM (2000) Opposing effects of protein kinase C and protein kinase A on metabotropic glutamate receptor signaling: selective desensitization of the inositol trisphosphate/Ca2+ pathway by phosphorylation of the receptor-G protein-coupling domain. Proc Natl Acad Sci U S A 97:6185–6190CrossRefGoogle Scholar
  35. Francesconi A, Kumari R, Zukin RS (2009) Regulation of group I metabotropic glutamate receptor trafficking and signaling by the caveolar/lipid raft pathway. J Neurosci: Off J Soc Neurosci 29:3590–3602CrossRefGoogle Scholar
  36. Gaborik Z, Hunyady L (2004) Intracellular trafficking of hormone receptors. Trends Endocrinol Metabol: TEM 15:286–293. CrossRefGoogle Scholar
  37. Gallagher SM, Daly CA, Bear MF, Huber KM (2004) Extracellular signal-regulated protein kinase activation is required for metabotropic glutamate receptor-dependent long-term depression in hippocampal area CA1. J Neurosci: Off J Soc Neurosci 24:4859–4864CrossRefGoogle Scholar
  38. Garland AM, Grady EF, Lovett M, Vigna SR, Frucht MM, Krause JE, Bunnett NW (1996) Mechanisms of desensitization and resensitization of G protein-coupled neurokinin1 and neurokinin2 receptors. Mol Pharmacol 49:438–446PubMedGoogle Scholar
  39. Gerber U, Gee CE, Benquet P (2007) Metabotropic glutamate receptors: intracellular signaling pathways. Curr Opin Pharmacol 7:56–61. CrossRefPubMedGoogle Scholar
  40. Gereau RW, Heinemann SF (1998) Role of protein kinase C phosphorylation in rapid desensitization of metabotropic glutamate receptor 5. Neuron 20:143–151CrossRefGoogle Scholar
  41. Gladding CM, Fitzjohn SM, Molnar E (2009) Metabotropic glutamate receptor-mediated long-term depression: molecular mechanisms. Pharmacol Rev 61:395–412CrossRefGoogle Scholar
  42. Goldgaber D, Lerman MI, McBride OW, Saffiotti U, Gajdusek DC (1987) Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science 235:877–880CrossRefGoogle Scholar
  43. Gulia R, Sharma R, Bhattacharyya S (2017) A critical role for ubiquitination in the endocytosis of glutamate receptors. J Biol Chem 292:1426–1437. CrossRefPubMedGoogle Scholar
  44. Hanyaloglu AC, von Zastrow M (2008) Regulation of GPCRs by endocytic membrane trafficking and its potential implications. Annu Rev Pharmacol Toxicol 48:537–568. CrossRefPubMedGoogle Scholar
  45. Harris SW et al (2008) Autism profiles of males with fragile X syndrome. Am J Ment Retard: AJMR 113:427–438. CrossRefPubMedGoogle Scholar
  46. Hicke L, Riezman H (1996) Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis. Cell 84:277–287CrossRefGoogle Scholar
  47. Hou L, Antion MD, Hu D, Spencer CM, Paylor R, Klann E (2006) Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression. Neuron 51:441–454CrossRefGoogle Scholar
  48. Huber KM, Gallagher SM, Warren ST, Bear MF (2002) Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci U S A 99:7746–7750CrossRefGoogle Scholar
  49. Iacovelli L et al (2003) Role of G protein-coupled receptor kinase 4 and beta-arrestin 1 in agonist-stimulated metabotropic glutamate receptor 1 internalization and activation of mitogen-activated protein kinases. J Biol Chem 278:12433–12442. CrossRefPubMedGoogle Scholar
  50. Kelly E, Bailey CP, Henderson G (2008) Agonist-selective mechanisms of GPCR desensitization. Br J Pharmacol 153(Suppl 1):S379–S388PubMedGoogle Scholar
  51. Kim CH, Lee J, Lee JY, Roche KW (2008) Metabotropic glutamate receptors: phosphorylation and receptor signaling. J Neurosci Res 86:1–10CrossRefGoogle Scholar
  52. Krupnick JG, Benovic JL (1998) The role of receptor kinases and arrestins in G protein-coupled receptor regulation. Annu Rev Pharmacol Toxicol 38:289–319CrossRefGoogle Scholar
  53. Lee JH et al (2008) Calmodulin dynamically regulates the trafficking of the metabotropic glutamate receptor mGluR5. Proc Natl Acad Sci U S A 105:12575–12580CrossRefGoogle Scholar
  54. Lee RK, Wurtman RJ, Cox AJ, Nitsch RM (1995) Amyloid precursor protein processing is stimulated by metabotropic glutamate receptors. Proc Natl Acad Sci U S A 92:8083–8087CrossRefGoogle Scholar
  55. Lefkowitz RJ, Shenoy SK (2005) Transduction of receptor signals by beta-arrestins. Science 308:512–517. CrossRefPubMedGoogle Scholar
  56. Li Z, Zhang Y, Ku L, Wilkinson KD, Warren ST, Feng Y (2001) The fragile X mental retardation protein inhibits translation via interacting with mRNA. Nucleic Acids Res 29:2276–2283CrossRefGoogle Scholar
  57. Lovinger DM (1996) Interactions between ethanol and agents that act on the NMDA-type glutamate receptor. Alcohol Clin Exp Res 20:187A–191ACrossRefGoogle Scholar
  58. Lujan R, Nusser Z, Roberts JD, Shigemoto R, Somogyi P (1996) Perisynaptic location of metabotropic glutamate receptors mGluR1 and mGluR5 on dendrites and dendritic spines in the rat hippocampus. Eur J Neurosci 8:1488–1500CrossRefGoogle Scholar
  59. Luscher C, Huber KM (2010) Group 1 mGluR-dependent synaptic long-term depression: mechanisms and implications for circuitry and disease. Neuron 65:445–459. CrossRefPubMedPubMedCentralGoogle Scholar
  60. Luttrell LM, Lefkowitz RJ (2002) The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals. J Cell Sci 115:455–465PubMedGoogle Scholar
  61. Mahato PK, Pandey S, Bhattacharyya S (2015) Differential effects of protein phosphatases in the recycling of metabotropic glutamate receptor 5. Neuroscience 306:138–150CrossRefGoogle Scholar
  62. Mannaioni G, Marino MJ, Valenti O, Traynelis SF, Conn PJ (2001) Metabotropic glutamate receptors 1 and 5 differentially regulate CA1 pyramidal cell function. J Neurosci: Off J Soc Neurosci 21:5925–5934CrossRefGoogle Scholar
  63. Marchese A, Benovic JL (2001) Agonist-promoted ubiquitination of the G protein-coupled receptor CXCR4 mediates lysosomal sorting. J Biol Chem 276:45509–45512. CrossRefPubMedGoogle Scholar
  64. Minakami R, Iida K, Hirakawa N, Sugiyama H (1995) The expression of two splice variants of metabotropic glutamate receptor subtype 5 in the rat brain and neuronal cells during development. J Neurochem 65:1536–1542CrossRefGoogle Scholar
  65. Minami K, Gereau RW, Minami M, Heinemann SF, Harris RA (1998) Effects of ethanol and anesthetics on type 1 and 5 metabotropic glutamate receptors expressed in Xenopus laevis oocytes. Mol Pharmacol 53:148–156CrossRefGoogle Scholar
  66. Mundell SJ, Matharu AL, Pula G, Roberts PJ, Kelly E (2001) Agonist-induced internalization of the metabotropic glutamate receptor 1a is arrestin- and dynamin-dependent. J Neurochem 78:546–551CrossRefGoogle Scholar
  67. Mundell SJ, Pula G, Carswell K, Roberts PJ, Kelly E (2003) Agonist-induced internalization of metabotropic glutamate receptor 1A: structural determinants for protein kinase C- and G protein-coupled receptor kinase-mediated internalization. J Neurochem 84:294–304CrossRefGoogle Scholar
  68. Mundell SJ, Pula G, More JC, Jane DE, Roberts PJ, Kelly E (2004) Activation of cyclic AMP-dependent protein kinase inhibits the desensitization and internalization of metabotropic glutamate receptors 1a and 1b. Mol Pharmacol 65:1507–1516. CrossRefPubMedGoogle Scholar
  69. Neve RL, Finch EA, Dawes LR (1988) Expression of the Alzheimer amyloid precursor gene transcripts in the human brain. Neuron 1:669–677CrossRefGoogle Scholar
  70. Niswender CM, Conn PJ (2010) Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 50:295–322CrossRefGoogle Scholar
  71. Nitsch RM, Slack BE, Wurtman RJ, Growdon JH (1992) Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. Science 258:304–307CrossRefGoogle Scholar
  72. Obara I et al (2009) Differential effects of chronic ethanol consumption and withdrawal on homer/glutamate receptor expression in subregions of the accumbens and amygdala of P rats. Alcohol Clin Exp Res 33:1924–1934. CrossRefPubMedPubMedCentralGoogle Scholar
  73. Oka A, Takashima S (1997) Induction of cyclo-oxygenase 2 in brains of patients with Down’s syndrome and dementia of Alzheimer type: specific localization in affected neurones and axons. Neuroreport 8:1161–1164CrossRefGoogle Scholar
  74. Oka A, Takashima S (1999) The up-regulation of metabotropic glutamate receptor 5 (mGluR5) in Down’s syndrome brains. Acta Neuropathol 97:275–278CrossRefGoogle Scholar
  75. Pandey S, Mahato PK, Bhattacharyya S (2014) Metabotropic glutamate receptor 1 recycles to the cell surface in protein phosphatase 2A-dependent manner in non-neuronal and neuronal cell lines. J Neurochem 131:602–614. CrossRefPubMedGoogle Scholar
  76. Parkitna JR et al (2013) Novelty-seeking behaviors and the escalation of alcohol drinking after abstinence in mice are controlled by metabotropic glutamate receptor 5 on neurons expressing dopamine d1 receptors. Biol Psychiatry 73:263–270. CrossRefPubMedGoogle Scholar
  77. Peavy RD, Conn PJ (1998) Phosphorylation of mitogen-activated protein kinase in cultured rat cortical glia by stimulation of metabotropic glutamate receptors. Journal of neurochemistry 71:603–612CrossRefGoogle Scholar
  78. Penagarikano O, Mulle JG, Warren ST (2007) The pathophysiology of fragile x syndrome. Annu Rev Genomics Hum Genet 8:109–129. CrossRefPubMedGoogle Scholar
  79. Pin JP, Duvoisin R (1995) The metabotropic glutamate receptors: structure and functions. Neuropharmacology 34:1–26CrossRefGoogle Scholar
  80. Pippig S, Andexinger S, Lohse MJ (1995) Sequestration and recycling of beta 2-adrenergic receptors permit receptor resensitization. Mol Pharmacol 47:666–676PubMedGoogle Scholar
  81. Pitcher JA, Payne ES, Csortos C, DePaoli-Roach AA, Lefkowitz RJ (1995) The G-protein-coupled receptor phosphatase: a protein phosphatase type 2A with a distinct subcellular distribution and substrate specificity. Proc Natl Acad Sci U S A 92:8343–8347CrossRefGoogle Scholar
  82. Pula G, Mundell SJ, Roberts PJ, Kelly E (2004) Agonist-independent internalization of metabotropic glutamate receptor 1a is arrestin- and clathrin-dependent and is suppressed by receptor inverse agonists. J Neurochem 89:1009–1020. CrossRefPubMedGoogle Scholar
  83. Rapacciuolo A, Suvarna S, Barki-Harrington L, Luttrell LM, Cong M, Lefkowitz RJ, Rockman HA (2003) Protein kinase A and G protein-coupled receptor kinase phosphorylation mediates beta-1 adrenergic receptor endocytosis through different pathways. J Biol Chem 278:35403–35411. CrossRefPubMedGoogle Scholar
  84. Ribeiro FM, Ferreira LT, Paquet M, Cregan T, Ding Q, Gros R, Ferguson SS (2009) Phosphorylation-independent regulation of metabotropic glutamate receptor 5 desensitization and internalization by G protein-coupled receptor kinase 2 in neurons. J Biol Chem 284:23444–23453. CrossRefPubMedPubMedCentralGoogle Scholar
  85. Romano C, Van den Pol AN, OMalley KL (1996) Enhanced early developmental expression of the metabotropic glutamate receptor mGluR5 in rat brain: protein, mRNA splice variants, and regional distribution. J Comp Neurol 367:403–412CrossRefGoogle Scholar
  86. Ronesi JA, Huber KM (2008) Metabotropic glutamate receptors and fragile x mental retardation protein: partners in translational regulation at the synapse. Sci Signal 1:pe6CrossRefGoogle Scholar
  87. Sallese M et al (2000) The G-protein-coupled receptor kinase GRK4 mediates homologous desensitization of metabotropic glutamate receptor 1. Faseb J 14:2569–2580CrossRefGoogle Scholar
  88. Schumann G et al (2008) Systematic analysis of glutamatergic neurotransmission genes in alcohol dependence and adolescent risky drinking behavior. Arch Gen Psychiatry 65:826–838. CrossRefPubMedGoogle Scholar
  89. Shenoy SK, McDonald PH, Kohout TA, Lefkowitz RJ (2001) Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin. Science 294:1307–1313. CrossRefPubMedGoogle Scholar
  90. Shigemoto R, Nakanishi S, Mizuno N (1992) Distribution of the mRNA for a metabotropic glutamate receptor (mGluR1) in the central nervous system: an in situ hybridization study in adult and developing rat. J Comp Neurol 322:121–135CrossRefGoogle Scholar
  91. Shigemoto R, Nomura S, Ohishi H, Sugihara H, Nakanishi S, Mizuno N (1993) Immunohistochemical localization of a metabotropic glutamate receptor, mGluR5, in the rat brain. Neurosci Lett 163:53–57CrossRefGoogle Scholar
  92. Sibley DR, Lefkowitz RJ (1985) Molecular mechanisms of receptor desensitization using the beta-adrenergic receptor-coupled adenylate cyclase system as a model. Nature 317:124–129CrossRefGoogle Scholar
  93. Sidhpura N, Weiss F, Martin-Fardon R (2010) Effects of the mGlu2/3 agonist LY379268 and the mGlu5 antagonist MTEP on ethanol seeking and reinforcement are differentially altered in rats with a history of ethanol dependence. Biol Psychiatry 67:804–811. CrossRefPubMedPubMedCentralGoogle Scholar
  94. Sinclair CM, Cleva RM, Hood LE, Olive MF, Gass JT (2012) mGluR5 receptors in the basolateral amygdala and nucleus accumbens regulate cue-induced reinstatement of ethanol-seeking behavior. Pharmacol Biochem Behav 101:329–335. CrossRefPubMedPubMedCentralGoogle Scholar
  95. Slack BE, Nitsch RM, Livneh E, Kunz GM Jr, Breu J, Eldar H, Wurtman RJ (1993) Regulation by phorbol esters of amyloid precursor protein release from Swiss 3T3 fibroblasts overexpressing protein kinase C alpha. J Biol Chem 268:21097–21101PubMedGoogle Scholar
  96. Sorensen SD, Conn PJ (2003) G protein-coupled receptor kinases regulate metabotropic glutamate receptor 5 function and expression. Neuropharmacology 44:699–706CrossRefGoogle Scholar
  97. Szumlinski KK, Ary AW, Lominac KD (2008) Homers regulate drug-induced neuroplasticity: implications for addiction. Biochem Pharmacol 75:112–133. CrossRefPubMedGoogle Scholar
  98. Szumlinski KK et al (2005) Homer2 is necessary for EtOH-induced neuroplasticity. J Neurosci: Off J Soc Neurosci 25:7054–7061. CrossRefGoogle Scholar
  99. Terrell J, Shih S, Dunn R, Hicke L (1998) A function for monoubiquitination in the internalization of a G protein-coupled receptor. Mol Cell 1:193–202CrossRefGoogle Scholar
  100. Trivedi RR, Bhattacharyya S (2012) Constitutive internalization and recycling of metabotropic glutamate receptor 5 (mGluR5). Biochem Biophys Res Commun 427:185–190CrossRefGoogle Scholar
  101. Tu JC et al (1998) Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors. Neuron 21:717–726CrossRefGoogle Scholar
  102. Urizar NL, Yang Z, Edenberg HJ, Davis RL (2007) Drosophila homer is required in a small set of neurons including the ellipsoid body for normal ethanol sensitivity and tolerance. J Neurosci:Off J Soc Neurosci 27:4541–4551. CrossRefGoogle Scholar
  103. Wang H, Zhuo M (2012) Group I metabotropic glutamate receptor-mediated gene transcription and implications for synaptic plasticity and diseases. Front Pharmacol 3:189. CrossRefPubMedPubMedCentralGoogle Scholar
  104. Winder DG, Conn PJ (1996) Roles of metabotropic glutamate receptors in glial function and glial-neuronal communication. J Neurosci Res 46:131–137CrossRefGoogle Scholar
  105. Wisniewski KE, Wisniewski HM, Wen GY (1985) Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down’s syndrome. Ann Neurol 17:278–282. CrossRefPubMedGoogle Scholar
  106. Yao HH, Ding JH, Zhou F, Wang F, Hu LF, Sun T, Hu G (2005) Enhancement of glutamate uptake mediates the neuroprotection exerted by activating group II or III metabotropic glutamate receptors on astrocytes. J Neurochem 92:948–961CrossRefGoogle Scholar
  107. Yu SS, Lefkowitz RJ, Hausdorff WP (1993) Beta-adrenergic receptor sequestration. A potential mechanism of receptor resensitization. J Biol Chem 268:337–341PubMedGoogle Scholar
  108. Zhang J, Ferguson SS, Barak LS, Menard L, Caron MG (1996) Dynamin and beta-arrestin reveal distinct mechanisms for G protein-coupled receptor internalization. J Biol Chem 271:18302–18305CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Prabhat Kumar Mahato
    • 1
  • Namrata Ramsakha
    • 1
  • Prachi Ojha
    • 1
  • Ravinder Gulia
    • 1
  • Rohan Sharma
    • 1
  • Samarjit Bhattacharyya
    • 1
    Email author
  1. 1.Department of Biological SciencesIndian Institute of Science Education and Research (IISER) MohaliSAS NagarIndia

Personalised recommendations