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Volume 2017 (2017), Article ID 5125624, 9 pages
https://doi.org/10.1155/2017/5125624
Review Article

Sustained Activity of Metabotropic Glutamate Receptor: Homer, Arrestin, and Beyond

1Department of Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea
2Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea
3Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea
4Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

Correspondence should be addressed to Sang Jeong Kim

Received 14 July 2017; Revised 10 October 2017; Accepted 31 October 2017; Published 21 November 2017

Academic Editor: Hee J. Chung

Copyright © 2017 Geehoon Chung and Sang Jeong Kim. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. C. M. Gladding, S. M. Fitzjohn, and E. Molnar, “Metabotropic glutamate receptor-mediated long-term depression: molecular mechanisms,” Pharmacological Reviews, vol. 61, no. 4, pp. 395–412, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. C. Lüscher and K. M. Huber, “Group 1 mGluR-dependent synaptic long-term depression: mechanisms and implications for circuitry and disease,” Neuron, vol. 65, no. 4, pp. 445–459, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. S. S. Willard and S. Koochekpour, “Glutamate, glutamate receptors, and downstream signaling pathways,” International Journal of Biological Sciences, vol. 9, no. 9, pp. 948–959, 2013. View at Publisher · View at Google Scholar · View at Scopus
  4. T. M. Piers, D. H. Kim, B. C. Kim, P. Regan, D. J. Whitcomb, and K. Cho, “Translational concepts of mGluR5 in synaptic diseases of the brain,” Frontiers in Pharmacology, vol. 3, p. 199, 2012. View at Publisher · View at Google Scholar · View at Scopus
  5. H. Wang and M. Zhuo, “Group I metabotropic glutamate receptor-mediated gene transcription and implications for synaptic plasticity and diseases,” Frontiers in Pharmacology, vol. 3, p. 189, 2012. View at Publisher · View at Google Scholar · View at Scopus
  6. C. M. Niswender and P. J. Conn, “Metabotropic glutamate receptors: physiology, pharmacology, and disease,” Annual Review of Pharmacology and Toxicology, vol. 50, no. 1, pp. 295–322, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. G. Corder, S. Doolen, R. R. Donahue et al., “Constitutive μ-opioid receptor activity leads to long-term endogenous analgesia and dependence,” Science, vol. 341, no. 6152, pp. 1394–1399, 2013. View at Publisher · View at Google Scholar · View at Scopus
  8. C. T. Gilliland, C. L. Salanga, T. Kawamura, J. Trejo, and T. M. Handel, “The chemokine receptor CCR1 is constitutively active, which leads to G protein-independent, β-arrestin-mediated internalization,” Journal of Biological Chemistry, vol. 288, no. 45, pp. 32194–32210, 2013. View at Publisher · View at Google Scholar · View at Scopus
  9. T. ARB, B. Plouffe, T. J. Cahill 3rd et al., “GPCR-G protein-β-arrestin super-complex mediates sustained G protein signaling,” Cell, vol. 166, no. 4, pp. 907–919, 2016. View at Publisher · View at Google Scholar · View at Scopus
  10. F. J. Meye, G. M. J. Ramakers, and R. A. H. Adan, “The vital role of constitutive GPCR activity in the mesolimbic dopamine system,” Translational Psychiatry, vol. 4, no. 2, p. e361, 2014. View at Publisher · View at Google Scholar · View at Scopus
  11. L. Fagni, F. Ango, L. Prezeau, P. F. Worley, J.-P. Pin, and J. Bockaert, “Control of constitutive activity of metabotropic glutamate receptors by Homer proteins,” International Congress Series, vol. 1249, pp. 245–251, 2003. View at Publisher · View at Google Scholar
  12. I. Panaccione, R. King, G. Molinaro et al., “Constitutively active group I mGlu receptors and PKMzeta regulate synaptic transmission in developing perirhinal cortex,” Neuropharmacology, vol. 66, pp. 143–150, 2013. View at Publisher · View at Google Scholar · View at Scopus
  13. F. Ango, L. Prézeau, T. Muller et al., “Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer,” Nature, vol. 411, pp. 962–965, 2001. View at Publisher · View at Google Scholar · View at Scopus
  14. S. R. Young, S.-C. Chuang, W. Zhao, R. K. S. Wong, and R. Bianchi, “Persistent receptor activity underlies group I mGluR-mediated cellular plasticity in CA3 neuron,” Journal of Neuroscience, vol. 33, no. 6, pp. 2526–2540, 2013. View at Publisher · View at Google Scholar · View at Scopus
  15. S. R. Young, R. Bianchi, and R. K. S. Wong, “Signaling mechanisms underlying group I mGluR-induced persistent AHP suppression in CA3 hippocampal neurons,” Journal of Neurophysiology, vol. 99, no. 3, pp. 1105–1118, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. L. J. Stoppel, B. D. Auerbach, R. K. Senter, A. R. Preza, R. J. Lefkowitz, and M. F. Bear, “β-Arrestin2 couples metabotropic glutamate receptor 5 to neuronal protein synthesis and is a potential target to treat fragile X,” Cell Reports, vol. 18, no. 12, pp. 2807–2814, 2017. View at Publisher · View at Google Scholar
  17. A. G. Eng, D. A. Kelver, T. P. Hedrick, and G. T. Swanson, “Transduction of group I mGluR-mediated synaptic plasticity by β-arrestin2 signalling,” Nature Communications, vol. 7, p. 13571, 2016. View at Publisher · View at Google Scholar · View at Scopus
  18. K. A. Newell and N. Matosin, “Rethinking metabotropic glutamate receptor 5 pathological findings in psychiatric disorders: implications for the future of novel therapeutics,” BMC Psychiatry, vol. 14, no. 1, p. 23, 2014. View at Publisher · View at Google Scholar · View at Scopus
  19. R. Bianchi, S.-C. Chuang, W. Zhao, S. R. Young, and R. K. S. Wong, “Cellular plasticity for group I mGluR-mediated epileptogenesis,” The Journal of Neuroscience, vol. 29, no. 11, pp. 3497–3507, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. T. J. Cahill 3rd, A. R. Thomsen, J. T. Tarrasch et al., “Distinct conformations of GPCR–β-arrestin complexes mediate desensitization, signaling, and endocytosis,” Proceedings of the National Academy of Sciences, vol. 114, no. 10, pp. 2562–2567, 2017. View at Publisher · View at Google Scholar
  21. S. L. Ritter and R. A. Hall, “Fine-tuning of GPCR activity by receptor-interacting proteins,” Nature Reviews Molecular Cell Biology, vol. 10, no. 12, pp. 819–830, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. D. Lodge, P. Tidball, M. S. Mercier et al., “Antagonists reversibly reverse chemical LTD induced by group I, group II and group III metabotropic glutamate receptors,” Neuropharmacology, vol. 74, pp. 135–146, 2013. View at Publisher · View at Google Scholar · View at Scopus
  23. N. C. Tronson, Y. F. Guzman, A. L. Guedea et al., “Metabotropic glutamate receptor 5/Homer interactions underlie stress effects on fear,” Biological Psychiatry, vol. 68, no. 11, pp. 1007–1015, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. K. Talavera, B. Nilius, and T. Voets, “Neuronal TRP channels: thermometers, pathfinders and life-savers,” Trends in Neurosciences, vol. 31, no. 6, pp. 287–295, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. H. Wang, B. Wang, K. P. Normoyle et al., “Brain temperature and its fundamental properties: a review for clinical neuroscientists,” Frontiers in Neuroscience, vol. 8, p. 307, 2014. View at Publisher · View at Google Scholar · View at Scopus
  26. M. G. Frank, “Circadian regulation of synaptic plasticity,” Biology, vol. 5, no. 3, 2016. View at Publisher · View at Google Scholar · View at Scopus
  27. J. A. Ronesi, K. A. Collins, S. A. Hays et al., “Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome,” Nature Neuroscience, vol. 15, no. 3, pp. 431–440, 2012. View at Publisher · View at Google Scholar · View at Scopus
  28. M. Yanagawa, T. Yamashita, and Y. Shichida, “Activation switch in the transmembrane domain of metabotropic glutamate receptor,” Molecular Pharmacology, vol. 76, no. 1, pp. 201–207, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. P. Malherbe, N. Kratochwil, F. Knoflach et al., “Mutational analysis and molecular modeling of the allosteric binding site of a novel, selective, noncompetitive antagonist of the metabotropic glutamate 1 receptor,” The Journal of Biological Chemistry, vol. 278, no. 10, pp. 8340–8347, 2003. View at Publisher · View at Google Scholar · View at Scopus
  30. B. Xiao, J. C. Tu, and P. F. Worley, “Homer: a link between neural activity and glutamate receptor function,” Current Opinion in Neurobiology, vol. 10, no. 3, pp. 370–374, 2000. View at Publisher · View at Google Scholar · View at Scopus
  31. B. Xiao, J. C. Tu, R. S. Petralia et al., “Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of Homer-related, synaptic proteins,” Neuron, vol. 21, no. 4, pp. 707–716, 1998. View at Publisher · View at Google Scholar · View at Scopus
  32. Y. Shiraishi-Yamaguchi and T. Furuichi, “The Homer family proteins,” Genome Biology, vol. 8, no. 2, p. 206, 2007. View at Publisher · View at Google Scholar · View at Scopus
  33. P. R. Brakeman, A. A. Lanahan, R. O'Brien et al., “Homer: a protein that selectively binds metabotropic glutamate receptors,” Nature, vol. 386, no. 6622, pp. 284–288, 1997. View at Publisher · View at Google Scholar · View at Scopus
  34. Y. Wang, W. Rao, C. Zhang et al., “Scaffolding protein Homer1a protects against NMDA-induced neuronal injury,” Cell Death and Disease, vol. 6, no. 8, p. e1843, 2015. View at Publisher · View at Google Scholar · View at Scopus
  35. K. Yamamoto, Y. Sakagami, S. Sugiura, K. Inokuchi, S. Shimohama, and N. Kato, “Homer 1a enhances spike-induced calcium influx via L-type calcium channels in neocortex pyramidal cells,” European Journal of Neuroscience, vol. 22, no. 6, pp. 1338–1348, 2005. View at Publisher · View at Google Scholar · View at Scopus
  36. Y. Sakagami, K. Yamamoto, S. Sugiura, K. Inokuchi, T. Hayashi, and N. Kato, “Essential roles of Homer-1a in homeostatic regulation of pyramidal cell excitability: a possible link to clinical benefits of electroconvulsive shock,” European Journal of Neuroscience, vol. 21, no. 12, pp. 3229–3239, 2005. View at Publisher · View at Google Scholar · View at Scopus
  37. L. Yang, L. Mao, Q. Tang, S. Samdani, Z. Liu, and J. Q. Wang, “A novel Ca2+−independent signaling pathway to extracellular signal-regulated protein kinase by coactivation of NMDA receptors and metabotropic glutamate receptor 5 in neurons,” Journal of Neuroscience, vol. 24, no. 48, pp. 10846–10857, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. L. Mao, L. Yang, Q. Tang, S. Samdani, G. Zhang, and J. Q. Wang, “The scaffold protein Homer1b/c links metabotropic glutamate receptor 5 to extracellular signal-regulated protein kinase cascades in neurons,” Journal of Neuroscience, vol. 25, no. 10, pp. 2741–2752, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. P. F. Worley, W. Zeng, G. Huang et al., “Homer proteins in Ca2+ signaling by excitable and non-excitable cells,” Cell Calcium, vol. 42, no. 4-5, pp. 363–371, 2007. View at Publisher · View at Google Scholar · View at Scopus
  40. A. Tappe, M. Klugmann, C. Luo et al., “Synaptic scaffolding protein Homer1a protects against chronic inflammatory pain,” Nature Medicine, vol. 12, no. 6, pp. 677–681, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. I. Minami, M. Kengaku, P. S. Smitt, R. Shigemoto, and T. Hirano, “Long-term potentiation of mGluR1 activity by depolarization-induced Homer1a in mouse cerebellar Purkinje neurons,” The European Journal of Neuroscience, vol. 17, no. 5, pp. 1023–1032, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. J. C. Tu, B. Xiao, J. P. Yuan et al., “Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors,” Neuron, vol. 21, no. 4, pp. 717–726, 1998. View at Publisher · View at Google Scholar · View at Scopus
  43. H. Abe, T. Misaka, M. Tateyama, and Y. Kubo, “Effects of coexpression with Homer isoforms on the function of metabotropic glutamate receptor 1α,” Molecular and Cellular Neurosciences, vol. 23, no. 2, pp. 157–168, 2003. View at Publisher · View at Google Scholar · View at Scopus
  44. J. H. Hu, L. Yang, P. J. Kammermeier et al., “Preso1 dynamically regulates group I metabotropic glutamate receptors,” Nature Neuroscience, vol. 15, no. 6, pp. 836–844, 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. P. Crépieux, A. Poupon, N. Langonné-Gallay et al., “A comprehensive view of the β-arrestinome,” Frontiers in Endocrinology, vol. 8, p. 32, 2017. View at Publisher · View at Google Scholar
  46. Y. K. Peterson and L. M. Luttrell, “The diverse roles of arrestin scaffolds in G protein–coupled receptor signaling,” Pharmacological Reviews, vol. 69, no. 3, pp. 256–297, 2017. View at Publisher · View at Google Scholar
  47. A. C. Magalhaes, H. Dunn, and S. S. G. S. Ferguson, “Regulation of GPCR activity, trafficking and localization by GPCR-interacting proteins,” British Journal of Pharmacology, vol. 165, no. 6, pp. 1717–1736, 2012. View at Publisher · View at Google Scholar · View at Scopus
  48. A. Eng, T. Hedrick, and G. Swanson, “mGluR1-β-arrestin 2 signaling mediates induction of excitatory synaptic plasticity,” The FASEB Journal, vol. 29, Supplement 1, pp. 934-935, 2015. View at Google Scholar
  49. P. Benquet, C. E. Gee, and U. Gerber, “Two distinct signaling pathways upregulate NMDA receptor responses via two distinct metabotropic glutamate receptor subtypes,” The Journal of Neuroscience, vol. 22, no. 22, pp. 9679–9686, 2002. View at Google Scholar
  50. U. Gerber, C. E. Gee, and P. Benquet, “Metabotropic glutamate receptors: intracellular signaling pathways,” Current Opinion in Pharmacology, vol. 7, no. 1, pp. 56–61, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. R. H. Oakley, S. A. Laporte, J. A. Holt, M. G. Caron, and L. S. Barak, “Differential affinities of visual arrestin, βarrestin1, and βarrestin2 for G protein-coupled receptors delineate two major classes of receptors,” Journal of Biological Chemistry, vol. 275, no. 22, pp. 17201–17210, 2000. View at Publisher · View at Google Scholar · View at Scopus
  52. G. W. Hubert, M. Paquet, and Y. Smith, “Differential subcellular localization of mGluR1a and mGluR5 in the rat and monkey substantia nigra,” The Journal of Neuroscience, vol. 21, no. 6, pp. 1838–1847, 2001. View at Google Scholar
  53. K. Vincent, V. M. Cornea, Y.-J. I. Jong et al., “Intracellular mGluR5 plays a critical role in neuropathic pain,” Nature Communications, vol. 7, article 10604, 2016. View at Publisher · View at Google Scholar · View at Scopus
  54. C. a Purgert, Y. Izumi, Y.-J. I. Jong, V. Kumar, C. F. Zorumski, and K. L. O’Malley, “Intracellular mGluR5 can mediate synaptic plasticity in the hippocampus,” The Journal of Neuroscience, vol. 34, no. 13, pp. 4589–4598, 2014. View at Publisher · View at Google Scholar · View at Scopus
  55. Y.-J. I. Jong, V. Kumar, and K. L. O’Malley, “Intracellular metabotropic glutamate receptor 5 (mGluR5) activates signaling cascades distinct from cell surface counterparts,” The Journal of Biological Chemistry, vol. 284, no. 51, pp. 35827–35838, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. V. Kumar, P. G. Fahey, Y.-J. I. Jong, N. Ramanan, and K. L. O’Malley, “Activation of intracellular metabotropic glutamate receptor 5 in striatal neurons leads to up-regulation of genes associated with sustained synaptic transmission including arc/Arg3.1 protein,” Journal of Biological Chemistry, vol. 287, no. 8, pp. 5412–5425, 2012. View at Publisher · View at Google Scholar · View at Scopus
  57. H. Eishingdrelo and S. Kongsamut, “Minireview: targeting GPCR activated ERK pathways for drug discovery,” Current Chemical Genomics and Translational Medicine, vol. 7, pp. 9–15, 2013. View at Publisher · View at Google Scholar
  58. B. Zimmerman, M. Simaan, M.-Y. Akoume et al., “Role of βarrestins in bradykinin B2 receptor-mediated signalling,” Cellular Signalling., vol. 23, no. 4, pp. 648–659, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. E. Cassier, N. Gallay, T. Bourquard et al., “Phosphorylation of β-arrestin2 at Thr383 by MEK underlies β-arrestin-dependent activation of Erk1/2 by GPCRs,” eLife, vol. 6, 2017. View at Publisher · View at Google Scholar
  60. E. Khoury, L. Nikolajev, M. Simaan, Y. Namkung, and S. A. Laporte, “Differential regulation of endosomal GPCR/β-arrestin complexes and trafficking by MAPK,” The Journal of Biological Chemistry, vol. 289, no. 34, pp. 23302–23317, 2014. View at Publisher · View at Google Scholar · View at Scopus
  61. A. Beautrait, J. S. Paradis, B. Zimmerman et al., “A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling,” Nature Communications, vol. 8, article 15054, 2017. View at Publisher · View at Google Scholar
  62. F. T. Lin, W. E. Miller, L. M. Luttrell, and R. J. Lefkowitz, “Feedback regulation of β-arrestin1 function by extracellular signal-regulated kinases,” The Journal of Biological Chemistry, vol. 274, no. 23, pp. 15971–15974, 1999. View at Publisher · View at Google Scholar · View at Scopus
  63. J. S. Paradis, S. Ly, É. Blondel-Tepaz et al., “Receptor sequestration in response to β-arrestin-2 phosphorylation by ERK1/2 governs steady-state levels of GPCR cell-surface expression,” Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 37, pp. E5160–E5168, 2015. View at Publisher · View at Google Scholar · View at Scopus
  64. S. M. Gallagher, C. A. Daly, M. F. Bear, and K. M. Huber, “Extracellular signal-regulated protein kinase activation is required for metabotropic glutamate receptor-dependent long-term depression in hippocampal area CA1,” The Journal of Neuroscience, vol. 24, no. 20, pp. 4859–4864, 2004. View at Publisher · View at Google Scholar · View at Scopus
  65. J. D. Sweatt, “Mitogen-activated protein kinases in synaptic plasticity and memory,” Current Opinion in Neurobiology, vol. 14, no. 3, pp. 311–317, 2004. View at Publisher · View at Google Scholar · View at Scopus
  66. R. J. Kelleher, A. Govindarajan, H.-Y. Jung, H. Kang, and S. Tonegawa, “Translational control by MAPK signaling in long-term synaptic plasticity and memory,” Cell, vol. 116, no. 3, pp. 467–479, 2004. View at Publisher · View at Google Scholar · View at Scopus
  67. S. Coffa, M. Breitman, S. M. Hanson et al., “The effect of arrestin conformation on the recruitment of c-Raf1, MEK1, and ERK1/2 activation,” PLoS One, vol. 6, no. 12, article e28723, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. L. M. Luttrell, F. L. Roudabush, E. W. Choy et al., “Activation and targeting of extracellular signal-regulated kinases by β-arrestin scaffolds,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 5, pp. 2449–2454, 2001. View at Publisher · View at Google Scholar · View at Scopus
  69. L.-M. Mao and J. Q. Wang, “Regulation of group I metabotropic glutamate receptors by MAPK/ERK in neurons,” Journal of Nature and Science, vol. 2, no. 12, 2016. View at Google Scholar
  70. L. R. Orlando, R. Ayala, L. R. Kett et al., “Phosphorylation of the homer-binding domain of group I metabotropic glutamate receptors by cyclin-dependent kinase 5,” Journal of Neurochemistry, vol. 110, no. 2, pp. 557–569, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. K. Rosenblum, M. Futter, K. Voss et al., “The role of extracellular regulated kinases I/II in late-phase long-term potentiation,” The Journal of Neuroscience, vol. 22, no. 13, pp. 5432–5441, 2002. View at Google Scholar
  72. S.-R. Jung, C. Kushmerick, J. B. Seo, D.-S. Koh, and B. Hille, “Muscarinic receptor regulates extracellular signal regulated kinase by two modes of arrestin binding,” Proceedings of the National Academy of Sciences, vol. 114, no. 28, pp. E5579–E5588, 2017. View at Publisher · View at Google Scholar
  73. E. K. Osterweil, D. D. Krueger, K. Reinhold, and M. F. Bear, “Hypersensitivity to mGluR5 and ERK1/2 leads to excessive protein synthesis in the hippocampus of a mouse model of fragile X syndrome,” The Journal of Neuroscience, vol. 30, no. 46, pp. 15616–15627, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. H.-H. Ryu and Y.-S. Lee, “Cell type-specific roles of RAS-MAPK signaling in learning and memory: implications in neurodevelopmental disorders,” Neurobiology of Learning and Memory, vol. 135, pp. 13–21, 2016. View at Publisher · View at Google Scholar · View at Scopus
  75. J. Min, “Molecular mechanism of beta-arrestin-dependent ERK activation downstream of protease-activated receptor-2,” 2011, http://www.escholarship.org/uc/item/95084710.
  76. J. A. Ronesi and K. M. Huber, “Homer interactions are necessary for metabotropic glutamate receptor-induced long-term depression and translational activation,” Journal of Neuroscience, vol. 28, no. 2, pp. 543–547, 2008. View at Publisher · View at Google Scholar · View at Scopus
  77. A. C. Emery, S. Pshenichkin, G. R. Takoudjou, E. Grajkowska, B. B. Wolfe, and J. T. Wroblewski, “The protective signaling of metabotropic glutamate receptor 1 is mediated by sustained, β-arrestin-1-dependent ERK phosphorylation,” Journal of Biological Chemistry, vol. 285, no. 34, pp. 26041–26048, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. R. Rong, J.-Y. Ahn, H. Huang et al., “PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis,” Nature Neuroscience, vol. 6, no. 11, pp. 1153–1161, 2003. View at Publisher · View at Google Scholar · View at Scopus
  79. A. Tappe-Theodor, Y. Fu, R. Kuner, and V. Neugebauer, “Homer1a signaling in the amygdala counteracts pain-related synaptic plasticity, mGluR1 function and pain behaviors,” Molecular Pain, vol. 7, p. 38, 2011. View at Publisher · View at Google Scholar · View at Scopus
  80. I. Obara, S. P. Goulding, J.-H. H. Hu, M. Klugmann, P. F. Worley, and K. K. Szumlinski, “Nerve injury-induced changes in Homer/glutamate receptor signaling contribute to the development and maintenance of neuropathic pain,” Pain, vol. 154, no. 10, pp. 1932–1945, 2013. View at Publisher · View at Google Scholar · View at Scopus
  81. K. K. Szumlinski, M. H. Dehoff, S. H. Kang et al., “Homer proteins regulate sensitivity to cocaine,” Neuron, vol. 43, no. 3, pp. 401–413, 2004. View at Publisher · View at Google Scholar · View at Scopus
  82. K. K. Szumlinski, K. E. Abernathy, E. B. Oleson et al., “Homer isoforms differentially regulate cocaine-induced neuroplasticity,” Neuropsychopharmacology, vol. 31, no. 4, pp. 768–777, 2006. View at Publisher · View at Google Scholar · View at Scopus