Palmitoylation regulates plasma membrane-nuclear shuttling of R7BP, a novel membrane anchor for the RGS7 family

The RGS7 (R7) family of RGS proteins bound to the divergent G beta subunit G beta 5 is a crucial regulator of G protein - coupled receptor ( GPCR) signaling in the visual and nervous systems. Here, we identify R7BP, a novel neuronally expressed protein that binds R7-G beta 5 complexes and shuttles them between the plasma membrane and nucleus. Regional expression of R7BP, G beta 5, and R7 isoforms in brain is highly coincident. R7BP is palmitoylated near its COOH terminus, which targets the protein to the plasma membrane. Depalmitoylation of R7BP translocates R7BP-R7-G beta 5 complexes from the plasma membrane to the nucleus. Compared with non-palmitoylated R7BP, palmitoylated R7BP greatly augments the ability of RGS7 to attenuate GPCR-mediated G protein regulated inward rectifying potassium channel activation. Thus, by controlling plasma membrane nuclear - shuttling of R7BP-R7-G beta 5 complexes, reversible palmitoylation of R7BP provides a novel mechanism that regulates GPCR signaling and potentially transduces signals directly from the plasma membrane to the nucleus.