Nuclear trafficking of regulator of G protein signaling proteins and their roles in the nucleus.

It was generally believed that the main function of regulator of G protein signaling (RGS) proteins was to negatively regulate GPCR (G protein-coupled receptor)-G protein signal transduction near the cell surface. Recent studies reveal that instead of localizing at the plasma membrane, where GPCRs and G proteins reside, many RGS proteins accumulate in the nucleus or shuttle between the cytoplasm and the nucleus. Some RGS proteins are even targeted to unique subnuclear regions. Nuclear trafficking of RGS proteins is controlled by nuclear localization signals and nuclear export signals. The RGS domain, which is essential for interaction between Gα subunits and RGS proteins, has also been shown to play an important role in nuclear trafficking of RGS proteins. This review focuses on the structural basis of RGS proteins and mechanisms underlying their nuclear trafficking, as well as their potential actions in the nucleus.