RGS proteins: lessons from the RGS9 subfamily

RGS proteins enhance the time resolution of G protein signaling cascades by accelerating GTP hydrolysis of G alpha subunits of heterotrimeric G proteins. RGS9-1, a photoreceptor-specific RGS protein, is the first vertebrate member of this sizeable family whose physiological function in a well-defined G protein pathway has been identified. It is essential for normal subsecond recovery kinetics of the light responses in retinal photoreceptors. Understanding this role allows RGS9-1 to serve as a useful model for understanding how specificity and regulation of RGS function are achieved. In addition to the catalytic RGS domain, shared among all members of this family, RGS9-1 contains several other domains, which are also found in a closely related subset of RGS proteins, the RGS9 subfamily. One of these domains, the G gamma-like (GGL) domain, has been identified as the attachment site for G beta 5 proteins, which act as obligate subunits for this subfamily. Results from RGS9-1 and other subfamily members suggest that specificity is achieved by cell type-specific transcription, RNA processing, and G beta 5-dependent protein stabilization. In addition, membrane localization via specific targeting domains likely plays an important role.