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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 alpha  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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Dynamic Regulation of RGS2 Suggests a Novel Mechanism in G-Protein Signaling and Neuronal Plasticity
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GTPase Activating Specificity of RGS12 and Binding Specificity of an Alternatively Spliced PDZ (PSD-95/Dlg/ZO-1) Domain
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E. J. Nestler and G. K. Aghajanian
Molecular and Cellular Basis of Addiction
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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
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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
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H. Chen and N. A. Lambert
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J.-H. Zhang and W. F. Simonds
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E. S. Park, C. O. Echetebu, S. Soloff, and M. S. Soloff
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