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PMID: 15534226 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

RGS9-2 modulates D2 dopamine receptor-mediated Ca2+ channel inhibition in rat striatal cholinergic interneurons.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 46 ·2004-11-16 ·Pages 16339-44

Cabrera-Vera TM, Hernandez S, Earls LR, Medkova M, Sundgren-Andersson AK, Surmeier DJ, Hamm HE

Abstract

Regulator of G protein signaling (RGS) proteins negatively regulate receptor-mediated second messenger responses by enhancing the GTPase activity of Galpha subunits. We describe a receptor-specific role for an RGS protein at the level of an individual brain neuron. RGS9-2 and Gbeta(5) mRNA and protein complexes were detected in striatal cholinergic and gamma-aminobutyric acidergic neurons. Dialysis of cholinergic neurons with RGS9 constructs enhanced basal Ca(2+) channel currents and reduced D(2) dopamine receptor modulation of Cav2.2 channels. These constructs did not alter M(2) muscarinic receptor modulation of Cav2.2 currents in the same neuron. The noncatalytic DEP-GGL domain of RGS9 antagonized endogenous RGS9-2 activity, enhancing D(2) receptor modulation of Ca(2+) currents. In vitro, RGS9 constructs accelerated GTPase activity, in agreement with electrophysiological measurements, and did so more effectively at Go than Gi. These results implicate RGS9-2 as a specific regulator of dopamine receptor-mediated signaling in the striatum and identify a role for GAP activity modulation by the DEP-GGL domain.

MeSH Terms
Animals Base Sequence Calcium Channels/drug effects,metabolism Cholinergic Fibers/drug effects,metabolism Corpus Striatum/drug effects,metabolism DNA/genetics GTP-Binding Protein beta Subunits/genetics,metabolism In Vitro Techniques Interneurons/drug effects,metabolism Protein Structure, Tertiary RGS Proteins/chemistry,genetics,metabolism,pharmacology RNA, Messenger/genetics,metabolism Rats Receptors, Dopamine D2/drug effects,metabolism Recombinant Proteins/chemistry,genetics,pharmacology Signal Transduction/drug effects
Chemicals
Calcium Channels GTP-Binding Protein beta Subunits Gnb5 protein, rat RGS Proteins RNA, Messenger Receptors, Dopamine D2 Recombinant Proteins regulator of g-protein signaling 9 DNA
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Cabrera-Vera Theresa M
Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Hernandez Salvador
Earls Laurie R
Medkova Martina
Sundgren-Andersson Anna K
Surmeier D James
Hamm Heidi E
References (43)
43 references, click to expand
  1. The alpha-helical domain of Galphat determines specific interaction with regulator of G protein signaling 9.
    J Biol Chem. 1999 Mar 26;274(13):8770-8 PMID: 10085118
  2. Cloning and characterization of RGS9-2: a striatal-enriched alternatively spliced product of the RGS9 gene.
    J Neurosci. 1999 Mar 15;19(6):2016-26 PMID: 10066255
  3. Fidelity of G protein beta-subunit association by the G protein gamma-subunit-like domains of RGS6, RGS7, and RGS11.
    Proc Natl Acad Sci U S A. 1999 May 25;96(11):6489-94 PMID: 10339615
  4. Delayed rectifier currents in rat globus pallidus neurons are attributable to Kv2.1 and Kv3.1/3.2 K(+) channels.
    J Neurosci. 1999 Aug 1;19(15):6394-404 PMID: 10414968
  5. Properties of Q-type calcium channels in neostriatal and cortical neurons are correlated with beta subunit expression.
    J Neurosci. 1999 Sep 1;19(17):7268-77 PMID: 10460233
  6. Regulators of G protein signaling 6 and 7. Purification of complexes with gbeta5 and assessment of their effects on g protein-mediated signaling pathways.
    J Biol Chem. 1999 Oct 22;274(43):31087-93 PMID: 10521509
  7. Structure, alternative splicing, and expression of the human RGS9 gene.
    Gene. 1999 Nov 15;240(1):23-34 PMID: 10564809
  8. RGS7 complex formation and colocalization with the Gbeta5 subunit in the adult rat brain and influence on Gbeta5gamma2-mediated PLCbeta signaling.
    J Neurosci Res. 2000 Apr 1;60(1):58-64 PMID: 10723068
  9. The regulator of G protein signaling family.
    Annu Rev Pharmacol Toxicol. 2000;40:235-71 PMID: 10836135
  10. Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens.
    Annu Rev Neurosci. 2000;23:185-215 PMID: 10845063
  11. GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins.
    Annu Rev Biochem. 2000;69:795-827 PMID: 10966476
  12. Modules in the photoreceptor RGS9-1.Gbeta 5L GTPase-accelerating protein complex control effector coupling, GTPase acceleration, protein folding, and stability.
    J Biol Chem. 2000 Nov 24;275(47):37093-100 PMID: 10978345
  13. D2 dopamine receptors in striatal medium spiny neurons reduce L-type Ca2+ currents and excitability via a novel PLC[beta]1-IP3-calcineurin-signaling cascade.
    J Neurosci. 2000 Dec 15;20(24):8987-95 PMID: 11124974
  14. Most central nervous system D2 dopamine receptors are coupled to their effectors by Go.
    Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3577-82 PMID: 11248120
  15. Regional distribution of regulators of G-protein signaling (RGS) 1, 2, 13, 14, 16, and GAIP messenger ribonucleic acids by in situ hybridization in rat brain.
    Brain Res Mol Brain Res. 2001 Mar 31;88(1-2):113-23 PMID: 11295237
  16. Allosteric modulation of Ca2+ channels by G proteins, voltage-dependent facilitation, protein kinase C, and Ca(v)beta subunits.
    Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4699-704 PMID: 11296298
  17. Regulator of G protein signaling proteins: novel multifunctional drug targets.
    J Pharmacol Exp Ther. 2001 Jun;297(3):837-45 PMID: 11356902
  18. Differential regulation of G protein-gated inwardly rectifying K(+) channel kinetics by distinct domains of RGS8.
    J Physiol. 2001 Sep 1;535(Pt 2):335-47 PMID: 11533127
  19. Direct interactions between the heterotrimeric G protein subunit G beta 5 and the G protein gamma subunit-like domain-containing regulator of G protein signaling 11: gain of function of cyan fluorescent protein-tagged G gamma 3.
    J Pharmacol Exp Ther. 2003 May;305(2):460-6 PMID: 12606627
  20. Instability of GGL domain-containing RGS proteins in mice lacking the G protein beta-subunit Gbeta5.
    Proc Natl Acad Sci U S A. 2003 May 27;100(11):6604-9 PMID: 12738888
  21. Specificity of G protein-RGS protein recognition is regulated by affinity adapters.
    Neuron. 2003 Jun 19;38(6):857-62 PMID: 12818172
  22. RGS9 modulates dopamine signaling in the basal ganglia.
    Neuron. 2003 Jun 19;38(6):941-52 PMID: 12818179
  23. The DEP domain determines subcellular targeting of the GTPase activating protein RGS9 in vivo.
    J Neurosci. 2003 Nov 12;23(32):10175-81 PMID: 14614075
  24. Differential effects of regulator of G protein signaling (RGS) proteins on serotonin 5-HT1A, 5-HT2A, and dopamine D2 receptor-mediated signaling and adenylyl cyclase activity.
    Cell Signal. 2004 Jun;16(6):711-21 PMID: 15093612
  25. RGS2 binds directly and selectively to the M1 muscarinic acetylcholine receptor third intracellular loop to modulate Gq/11alpha signaling.
    J Biol Chem. 2004 May 14;279(20):21248-56 PMID: 14976183
  26. Neurotransmitter inhibition of neuronal calcium currents by changes in channel voltage dependence.
    Nature. 1989 Jul 13;340(6229):153-6 PMID: 2567963
  27. Muscarinic receptor activation attenuates D2 dopamine receptor mediated inhibition of acetylcholine release in rat striatum: indications for a common signal transduction pathway.
    Neuroscience. 1990;37(1):1-9 PMID: 1978737
  28. The neostriatal mosaic: multiple levels of compartmental organization.
    J Neural Transm Suppl. 1992;36:43-59 PMID: 1527520
  29. Dopamine receptor subtypes colocalize in rat striatonigral neurons.
    Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10178-82 PMID: 1332033
  30. Modulation of Ca2+ channels by protein kinase C in rat central and peripheral neurons: disruption of G protein-mediated inhibition.
    Neuron. 1993 Aug;11(2):305-20 PMID: 8102534
  31. Voltage-dependent modulation of N-type calcium channels by G-protein beta gamma subunits.
    Nature. 1996 Mar 21;380(6571):255-8 PMID: 8637575
  32. Modulation of Ca2+ channels by G-protein beta gamma subunits.
    Nature. 1996 Mar 21;380(6571):258-62 PMID: 8637576
  33. The GTPase-activating protein RGS4 stabilizes the transition state for nucleotide hydrolysis.
    J Biol Chem. 1996 Nov 1;271(44):27209-12 PMID: 8910288
  34. D2 dopamine receptors reduce N-type Ca2+ currents in rat neostriatal cholinergic interneurons through a membrane-delimited, protein-kinase-C-insensitive pathway.
    J Neurophysiol. 1997 Feb;77(2):1003-15 PMID: 9065864
  35. Regulators of G-protein signaling (RGS) proteins: region-specific expression of nine subtypes in rat brain.
    J Neurosci. 1997 Oct 15;17(20):8024-37 PMID: 9315921
  36. Coordinated expression of dopamine receptors in neostriatal medium spiny neurons.
    Adv Pharmacol. 1998;42:1020-3 PMID: 9328072
  37. RGS9, a GTPase accelerator for phototransduction.
    Neuron. 1998 Jan;20(1):95-102 PMID: 9459445
  38. RGS9: a regulator of G-protein signalling with specific expression in rat and mouse striatum.
    J Neurosci Res. 1998 Apr 1;52(1):118-24 PMID: 9556034
  39. Molecular characterization of human and rat RGS 9L, a novel splice variant enriched in dopamine target regions, and chromosomal localization of the RGS 9 gene.
    Mol Pharmacol. 1998 Oct;54(4):687-94 PMID: 9765512
  40. A G protein gamma subunit-like domain shared between RGS11 and other RGS proteins specifies binding to Gbeta5 subunits.
    Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13307-12 PMID: 9789084
  41. The N-terminal domain of RGS4 confers receptor-selective inhibition of G protein signaling.
    J Biol Chem. 1998 Dec 25;273(52):34687-90 PMID: 9856989
  42. RGS proteins determine signaling specificity of Gq-coupled receptors.
    J Biol Chem. 1999 Feb 5;274(6):3549-56 PMID: 9920901
  43. Regulators of G protein signaling proteins as determinants of the rate of desensitization of presynaptic calcium channels.
    J Biol Chem. 1999 May 14;274(20):14490-4 PMID: 10318875
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0407416101
Published
2004-11-16
Epub
2004-00-08
Pages
16339-44
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC528982
Subset
IM
Grants
NINDS NIH HHS · R01 NS034696 · United States
NEI NIH HHS · EY10291 · United States
NIDA NIH HHS · R01 DA012958 · United States
NINDS NIH HHS · 1F32NS10955-01 · United States
NINDS NIH HHS · NS34696 · United States
NEI NIH HHS · EY06062 · United States
NINDS NIH HHS · R37 NS034696 · United States
NEI NIH HHS · R01 EY010291 · United States
NEI NIH HHS · R01 EY006062 · United States
NCI NIH HHS · T32 CA070085 · United States
NCI NIH HHS · 5T32CA70085 · United States
NIDA NIH HHS · DA12958 · United States
NINDS NIH HHS · F32 NS010955 · United States
External Links
PubMed source DOI: 10.1073/pnas.0407416101 PMC Full Text View journal details
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