“…Some cellular mechanisms contributing to RGS membrane targeting have previously been identified. Plasma membrane recruitment of RGS proteins can occur as a result of G protein activation (11,12), enhanced expression of specific unactivated G␣ subunits or GPCRs (1,2,13), intrinsic transmembrane-spanning regions (3,4,14), post-translational lipid modifications (5,15), or electrostatic interactions with membrane lipids (6,16) or via scaffolding proteins (6,7). Specific domains, namely the disheveled, Egl-10, and pleckstrin (DEP) domains within some RGS proteins, can interact directly with internal loop regions (8,17) and the intracellular C-terminal tail of GPCRs to promote selectivity of RGS activity at the plasma membrane (9,18).…”