PT  - JOURNAL ARTICLE
AU  - Z. Rahman
AU  - S. J. Gold
AU  - M. N. Potenza
AU  - C. W. Cowan
AU  - Y. G. Ni
AU  - W. He
AU  - T. G. Wensel
AU  - E. J. Nestler
TI  - Cloning and Characterization of RGS9-2: A Striatal-Enriched Alternatively Spliced Product of the RGS9 Gene
AID  - 10.1523/JNEUROSCI.19-06-02016.1999
DP  - 1999 Mar 15
TA  - The Journal of Neuroscience
PG  - 2016--2026
VI  - 19
IP  - 6
4099  - http://www.jneurosci.org/content/19/6/2016.short
4100  - http://www.jneurosci.org/content/19/6/2016.full
SO  - J. Neurosci.1999 Mar 15; 19
AB  - Regulators of G-protein signaling (RGS) proteins act as GTPase-activating proteins (GAPs) for α 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 (Gαt) 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.