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Volume 17, Number 20,
Issue of October 15, 1997
pp. 8024-8037
Copyright ©1997 Society for Neuroscience
Regulators of G-Protein Signaling (RGS) Proteins: Region-Specific
Expression of Nine Subtypes in Rat Brain
Received May 29, 1997; revised Aug. 1, 1997; accepted Aug. 5, 1997.
Stephen J. Gold1, 2,
Yan G. Ni1, 2,
Henrik G. Dohlman3, and
Eric J. Nestler1, 2, 3
1 Laboratory of Molecular Psychiatry and Departments of
2 Psychiatry and 3 Pharmacology, Yale
University School of Medicine, New Haven, Connecticut 06508
The recently discovered regulators of G-protein signaling (RGS)
proteins potently modulate the functioning of heterotrimeric G-proteins
by stimulating the GTPase activity of G-protein subunits. The mRNAs
for numerous subtypes of putative RGS proteins have been identified in
mammalian tissues, but little is known about their expression in brain.
We performed a systematic survey of the localization of mRNAs encoding
nine of these RGSs, RGS3-RGS11, in brain by in situ
hybridization. Striking region-specific patterns of expression were
observed. Five subtypes, RGS4, RGS7, RGS8, RGS9, and RGS10 mRNAs, are
densely expressed in brain, whereas the other subtypes (RGS3, RGS5,
RGS6, and RGS11) are expressed at lower density and in more restricted
regions. RGS4 mRNA is notable for its dense expression in neocortex,
piriform cortex, caudoputamen, and ventrobasal thalamus. RGS8 mRNA is
highly expressed in the cerebellar Purkinje cell layer as well as in
several midbrain nuclei. RGS9 mRNA is remarkable for its nearly
exclusive enrichment in striatal regions. RGS10 mRNA is densely
expressed in dentate gyrus granule cells, superficial layers of
neocortex, and dorsal raphe. To assess whether the expression of RGS
mRNAs can be regulated, we examined the effect of an acute seizure on
levels of RGS7, RGS8, and RGS10 mRNAs in hippocampus. Of the three
subtypes, changes in RGS10 levels were most pronounced, decreasing by
~40% in a time-dependent manner in response to a single seizure.
These results, which document highly specific patterns of RGS mRNA
expression in brain and their ability to be regulated in a dynamic
manner, support the view that RGS proteins may play an important role in determining the intensity and specificity of signaling pathways in
brain as well as their adaptations to synaptic activity.
Key words:
seizure;
gene expression;
striatum;
neocortex;
GTPase-activating proteins;
Sst2;
GAIP
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K. Melliti, U. Meza, R. Fisher, and B. Adams
Regulators of G Protein Signaling Attenuate the G Protein-mediated Inhibition of N-Type Ca Channels
J. Gen. Physiol.,
January 1, 1999;
113(1):
97 - 110.
[Abstract]
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V. A. Boundy, S. J. Gold, C. J. Messer, J. Chen, J. H. Son, T. H. Joh, and E. J. Nestler
Regulation of Tyrosine Hydroxylase Promoter Activity by Chronic Morphine in TH9.0-LacZ Transgenic Mice
J. Neurosci.,
December 1, 1998;
18(23):
9989 - 9995.
[Abstract]
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B. E. Snow, A. M. Krumins, G. M. Brothers, S.-F. Lee, M. A. Wall, S. Chung, J. Mangion, S. Arya, A. G. Gilman, and D. P. Siderovski
A G protein gamma subunit-like domain shared between RGS11 and other RGS proteins specifies binding to Gbeta 5 subunits
PNAS,
October 27, 1998;
95(22):
13307 - 13312.
[Abstract]
[Full Text]
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J. L. Glick, T. E. Meigs, A. Miron, and P. J. Casey
RGSZ1, a Gz-selective Regulator of G Protein Signaling Whose Action Is Sensitive to the Phosphorylation State of Gzalpha
J. Biol. Chem.,
October 2, 1998;
273(40):
26008 - 26013.
[Abstract]
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J. G. Granneman, Y. Zhai, Z. Zhu, M. J. Bannon, S. A. Burchett, C. J. Schmidt, R. Andrade, and J. Cooper
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.,
October 1, 1998;
54(4):
687 - 694.
[Abstract]
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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]
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K. M. Druey, B. M. Sullivan, D. Brown, E. R. Fischer, N. Watson, K. J. Blumer, C. R. Gerfen, A. Scheschonka, and J. H. Kehrl
Expression of GTPase-deficient Gialpha 2 Results in Translocation of Cytoplasmic RGS4 to the Plasma Membrane
J. Biol. Chem.,
July 17, 1998;
273(29):
18405 - 18410.
[Abstract]
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B. E. Snow, R. A. Hall, A. M. Krumins, G. M. Brothers, D. Bouchard, C. A. Brothers, S. Chung, J. Mangion, A. G. Gilman, R. J. Lefkowitz, et al.
GTPase Activating Specificity of RGS12 and Binding Specificity of an Alternatively Spliced PDZ (PSD-95/Dlg/ZO-1) Domain
J. Biol. Chem.,
July 10, 1998;
273(28):
17749 - 17755.
[Abstract]
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E. J. Nestler and G. K. Aghajanian
Molecular and Cellular Basis of Addiction
Science,
October 3, 1997;
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58 - 63.
[Abstract]
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D. S. Witherow, Q. Wang, K. Levay, J. L. Cabrera, J. Chen, G. B. Willars, and V. Z. Slepak
Complexes of the G Protein Subunit Gbeta 5 with the Regulators of G Protein Signaling RGS7 and RGS9. CHARACTERIZATION IN NATIVE TISSUES AND IN TRANSFECTED CELLS
J. Biol. Chem.,
August 4, 2000;
275(32):
24872 - 24880.
[Abstract]
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A. Cavalli, K. M. Druey, and G. Milligan
The Regulator of G Protein Signaling RGS4 Selectively Enhances alpha 2A-Adreoreceptor Stimulation of the GTPase Activity of Go1alpha and Gi2alpha
J. Biol. Chem.,
July 28, 2000;
275(31):
23693 - 23699.
[Abstract]
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A. J. Eisch, M. Barrot, C. A. Schad, D. W. Self, and E. J. Nestler
Opiates inhibit neurogenesis in the adult rat hippocampus
PNAS,
June 20, 2000;
97(13):
7579 - 7584.
[Abstract]
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H. Chen and N. A. Lambert
Endogenous regulators of G protein signaling proteins regulate presynaptic inhibition at rat hippocampal synapses
PNAS,
November 7, 2000;
97(23):
12810 - 12815.
[Abstract]
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J.-H. Zhang and W. F. Simonds
Copurification of Brain G-Protein beta 5 with RGS6 and RGS7
J. Neurosci.,
February 1, 2000;
20(3):
RC59 - RC59.
[Abstract]
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E. S. Park, C. O. Echetebu, S. Soloff, and M. S. Soloff
Oxytocin stimulation of RGS2 mRNA expression in cultured human myometrial cells
Am J Physiol Endocrinol Metab,
March 1, 2002;
282(3):
E580 - E584.
[Abstract]
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