QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (62) Citing Articles via Google Scholar Google Scholar Articles by Saugstad, J. A. Articles by Conn, P. J. Search for Related Content PubMed PubMed Citation Articles by Saugstad, J. A. Articles by Conn, P. J.

 Previous Article  |  Next Article 

The Journal of Neuroscience, February 1, 1998, 18(3):905-913

RGS4 Inhibits Signaling by Group I Metabotropic Glutamate Receptors

Julie A. Saugstad, Michael J. Marino, Julie A. Folk, John R. Hepler, and P. Jeffrey Conn

Department of Pharmacology, Emory University, Atlanta, Georgia 30322

Metabotropic glutamate receptors (mGluRs) couple to heterotrimeric G-proteins and regulate cell excitability and synaptic transmission in the CNS. Considerable effort has been focused on understanding the cellular and biochemical mechanisms that underlie regulation of signaling by G-proteins and their linked receptors, including the mGluRs. Recent findings demonstrate that regulators of G-protein signaling (RGS) proteins act as effector antagonists and GTPase-activating proteins for G subunits to inhibit cellular responses by G-protein-coupled receptors. RGS4 blocks G_q activation of phospholipase C and is expressed broadly in rat brain. The group I mGluRs (mGluRs 1 and 5) couple to G_q pathways to regulate several effectors in the CNS. We examined the capacity of RGS4 to regulate group I mGluR responses. In Xenopus oocytes, purified RGS4 virtually abolishes the mGluR1a- and mGluR5a-mediated but not the inositol trisphospate-mediated activation of a calcium-dependent chloride current. Additionally, RGS4 markedly attenuates the mGluR5-mediated inhibition of potassium currents in hippocampal CA1 neurons. This inhibition is dose-dependent and occurs at concentrations that are virtually identical to those required for inhibition of phospholipase C activity in NG108-15 membranes and reconstituted systems using purified proteins. These findings demonstrate that RGS4 can modulate mGluR responses in neurons, and they highlight a previously unknown mechanism for regulation of G-protein-coupled receptor signaling in the CNS.

Key words: RGS4; RGS proteins; metabotropic glutamate receptor; hippocampus; G-proteins; synaptic regulation; Xenopus

---

Copyright © 1998 Society for Neuroscience  0270-6474/98/183905-09$05.00/0

This article has been cited by other articles:

				M. Schwendt and J. F. McGinty Regulator of G-Protein Signaling 4 Interacts with Metabotropic Glutamate Receptor Subtype 5 in Rat Striatum: Relevance to Amphetamine Behavioral Sensitization J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 650 - 657. [Abstract] [Full Text] [PDF]

				S. Yang and Y.-P. Li RGS10-null mutation impairs osteoclast differentiation resulting from the loss of [Ca2+]i oscillation regulation Genes & Dev., July 15, 2007; 21(14): 1803 - 1816. [Abstract] [Full Text] [PDF]

				J. W. Buckholtz, A. Meyer-Lindenberg, R. A. Honea, R. E. Straub, L. Pezawas, M. F. Egan, R. Vakkalanka, B. Kolachana, B. A. Verchinski, S. Sust, et al. Allelic Variation in RGS4 Impacts Functional and Structural Connectivity in the Human Brain J. Neurosci., February 14, 2007; 27(7): 1584 - 1593. [Abstract] [Full Text] [PDF]

				H. Homayoun and B. Moghaddam Bursting of Prefrontal Cortex Neurons in Awake Rats is Regulated by Metabotropic Glutamate 5 (mGlu5) Receptors: Rate-dependent Influence and Interaction with NMDA Receptors Cereb Cortex, January 1, 2006; 16(1): 93 - 105. [Abstract] [Full Text] [PDF]

				L. Calo, V. Bruno, P. Spinsanti, G. Molinari, V. Korkhov, Z. Esposito, M. Patane, D. Melchiorri, M. Freissmuth, and F. Nicoletti Interactions between Ephrin-B and Metabotropic Glutamate 1 Receptors in Brain Tissue and Cultured Neurons J. Neurosci., March 2, 2005; 25(9): 2245 - 2254. [Abstract] [Full Text] [PDF]

				G. K. Dhami, L. B. Dale, P. H. Anborgh, K. E. O'Connor-Halligan, R. Sterne-Marr, and S. S. G. Ferguson G Protein-coupled Receptor Kinase 2 Regulator of G Protein Signaling Homology Domain Binds to Both Metabotropic Glutamate Receptor 1a and G{alpha}q to Attenuate Signaling J. Biol. Chem., April 16, 2004; 279(16): 16614 - 16620. [Abstract] [Full Text] [PDF]

				E. T. Bodor, G. L. Waldo, S. B. Hooks, J. Corbitt, J. L. Boyer, and T. K. Harden Purification and Functional Reconstitution of the Human P2Y12 Receptor Mol. Pharmacol., November 1, 2003; 64(5): 1210 - 1216. [Abstract] [Full Text] [PDF]

				L. Iacovelli, L. Salvatore, L. Capobianco, A. Picascia, E. Barletta, M. Storto, S. Mariggio, M. Sallese, A. Porcellini, F. Nicoletti, et al. 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., March 28, 2003; 278(14): 12433 - 12442. [Abstract] [Full Text] [PDF]

				M. Garnier, P. F. Zaratin, G. Ficalora, M. Valente, L. Fontanella, M.-H. Rhee, K. J. Blumer, and M. A. Scheideler Up-Regulation of Regulator of G Protein Signaling 4 Expression in a Model of Neuropathic Pain and Insensitivity to Morphine J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 1299 - 1306. [Abstract] [Full Text] [PDF]

				H. Zhong, S. M. Wade, P. J. Woolf, J. J. Linderman, J. R. Traynor, and R. R. Neubig A Spatial Focusing Model for G Protein Signals. REGULATOR OF G PROTEIN SIGNALING (RGS) PROTEIN-MEDIATED KINETIC SCAFFOLDING J. Biol. Chem., February 21, 2003; 278(9): 7278 - 7284. [Abstract] [Full Text] [PDF]

				M.-C. Nlend, R. J. Bookman, G. E. Conner, and M. Salathe Regulator of G-Protein Signaling Protein 2 Modulates Purinergic Calcium and Ciliary Beat Frequency Responses in Airway Epithelia Am. J. Respir. Cell Mol. Biol., October 1, 2002; 27(4): 436 - 445. [Abstract] [Full Text] [PDF]

				D. R. Ireland and W. C. Abraham Group I mGluRs Increase Excitability of Hippocampal CA1 Pyramidal Neurons by a PLC-Independent Mechanism J Neurophysiol, July 1, 2002; 88(1): 107 - 116. [Abstract] [Full Text] [PDF]

				E. Bracci, M. Vreugdenhil, S. P. Hack, and J. G. R. Jefferys Dynamic Modulation of Excitation and Inhibition During Stimulation at Gamma and Beta Frequencies in the CA1 Hippocampal Region J Neurophysiol, June 1, 2001; 85(6): 2412 - 2422. [Abstract] [Full Text] [PDF]

				A. Tozzi, E. Guatteo, L. Caputi, G. Bernardi, and N. B. Mercuri Group I mGluRs Coupled to G Proteins Are Regulated by Tyrosine Kinase in Dopamine Neurons of the Rat Midbrain J Neurophysiol, June 1, 2001; 85(6): 2490 - 2497. [Abstract] [Full Text] [PDF]

				V. Neugebauer, P.-S. Chen, and W. D. Willis Groups II and III Metabotropic Glutamate Receptors Differentially Modulate Brief and Prolonged Nociception in Primate STT Cells J Neurophysiol, December 1, 2000; 84(6): 2998 - 3009. [Abstract] [Full Text] [PDF]

				M. SALLESE, L. SALVATORE, E. D’URBANO, G. SALA, M. STORTO, T. LAUNEY, F. NICOLETTI, T. KNÖPFEL, and A. DE BLASI The G-protein-coupled receptor kinase GRK4 mediates homologous desensitization of metabotropic glutamate receptor 1 FASEB J, December 1, 2000; 14(15): 2569 - 2580. [Abstract] [Full Text]

				A. Francesconi and R. M. Duvoisin 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 PNAS, May 23, 2000; 97(11): 6185 - 6190. [Abstract] [Full Text] [PDF]

				E. Kim, T. Arnould, L. Sellin, T. Benzing, N. Comella, O. Kocher, L. Tsiokas, V. P. Sukhatme, and G. Walz Interaction between RGS7 and polycystin PNAS, May 25, 1999; 96(11): 6371 - 6376. [Abstract] [Full Text] [PDF]

				M. A. Diverse-Pierluissi, T. Fischer, J. D. Jordan, M. Schiff, D. F. Ortiz, M. G. Farquhar, and L. De Vries Regulators of G Protein Signaling Proteins as Determinants of the Rate of Desensitization of Presynaptic Calcium Channels J. Biol. Chem., May 14, 1999; 274(20): 14490 - 14494. [Abstract] [Full Text] [PDF]

				Z. Rahman, S. J. Gold, M. N. Potenza, C. W. Cowan, Y. G. Ni, W. He, T. G. Wensel, and E. J. Nestler Cloning and Characterization of RGS9-2: A Striatal-Enriched Alternatively Spliced Product of the RGS9 Gene J. Neurosci., March 15, 1999; 19(6): 2016 - 2026. [Abstract] [Full Text] [PDF]

				X. Xu, W. Zeng, S. Popov, D. M. Berman, I. Davignon, K. Yu, D. Yowe, S. Offermanns, S. Muallem, and T. M. Wilkie RGS Proteins Determine Signaling Specificity of Gq-coupled Receptors J. Biol. Chem., February 5, 1999; 274(6): 3549 - 3556. [Abstract] [Full Text] [PDF]

				T. Ingi, A. M. Krumins, P. Chidiac, G. M. Brothers, S. Chung, B. E. Snow, C. A. Barnes, A. A. Lanahan, D. P. Siderovski, E. M. Ross, et al. Dynamic Regulation of RGS2 Suggests a Novel Mechanism in G-Protein Signaling and Neuronal Plasticity J. Neurosci., September 15, 1998; 18(18): 7178 - 7188. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help