RGS proteins comprise a large family of proteins that contain over 37 different members [12]. Each RGS protein has a conserved 120 amino acid core domain, commonly called the RGS domain, which is responsible for the GAP activity [14,15]. RGS proteins are widely expressed throughout the brain, where they can potentially modulate GPCR-mediated signaling [16]. Individual RGS proteins interact with particular Gα subunits, which may be determined by specific sequences in the RGS domain, their selective expression, and the corresponding Gα subunit. For example, two RGS9 splice variants, RGS9-1 and RGS9-2, differ only in the C terminal tail, which confers selectivity with interaction proteins [17]. In addition, cell-type specific expression distinguishes the splice variants. RGS9-1 is observed almost exclusively in the retina and is responsible for acceleration of hydrolysis of GTP by Gαt. RGS9-2, in turn, is strongly expressed in the striatum and regulates D2 dopamine and µ-opioid receptors coupled to Gαi/o [18]. Thus, the combination of cell-specific expression and selective protein-protein association for different RGS proteins suggest key functional roles for specific RGS proteins in the brain.
