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The Journal of Neuroscience, March 15, 1999, 19(6):2016-2026
Cloning and Characterization of RGS9-2: A Striatal-Enriched
Alternatively Spliced Product of the RGS9 Gene
Z.
Rahman1, 2,
S. J.
Gold2,
M. N.
Potenza2,
C. W.
Cowan3, 4,
Y. G.
Ni2,
W.
He4,
T. G.
Wensel3, 4, and
E. J.
Nestler2
1 Department of Molecular, Cellular and Developmental
Biology, 2 Laboratory of Molecular Psychiatry, Yale
University, New Haven, Connecticut 06508, and 3 Program in
Cell and Molecular Biology, 4 Verna and Marrs McLean
Department of Biochemistry, Baylor College of Medicine, Houston, Texas
77030
Regulators of G-protein signaling (RGS) proteins act as
GTPase-activating proteins (GAPs) for  subunits of heterotrimeric G-proteins. Previous in situ hybridization analysis of
mRNAs encoding RGS3-RGS11 revealed region-specific expression patterns
in rat brain. RGS9 showed a particularly striking pattern of almost
exclusive enrichment in striatum. In a parallel study, RGS9 cDNA, here
referred to as RGS9-1, was cloned from retinal cDNA libraries, and the encoded protein was identified as a GAP for transducin
(Gt) in rod outer segments. In the present study
we identify a novel splice variant of RGS9, RGS9-2, cloned from a mouse
forebrain cDNA library, which encodes a striatal-specific isoform of
the protein. RGS9-2 is 191 amino acids longer than the retinal isoform,
has a unique 3' untranslated region, and is highly enriched in
striatum, with much lower levels seen in other brain regions and no
expression detectable in retina. Immunohistochemistry showed that
RGS9-2 protein is restricted to striatal neuropil and absent in
striatal terminal fields. The functional activity of RGS9-2 is
supported by the finding that it, but not RGS9-1, dampens the
Gi/o-coupled µ-opioid receptor response in
vitro. Characterization of a bacterial artificial chromosome
genomic clone of ~200 kb indicates that these isoforms represent
alternatively spliced mRNAs from a single gene and that the RGS domain,
conserved among all known RGS members, is encoded over three distinct
exons. The distinct C-terminal domains of RGS9-2 and RGS9-1 presumably
contribute to unique regulatory properties in the neural and retinal
cells in which these proteins are selectively expressed.
Key words:
striatum; transducin; alternative splicing; µ-opioid
receptor; GTPase-activating proteins; retina
Copyright © 1999 Society for Neuroscience 0270-6474/99/1962016-11$05.00/0
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