• Ryan M Drenan, Craig A Doupnik, Muralidharan Jayaraman, Abigail L Buchwalter, Kevin M Kaltenbronn, James E Huettner, Maurine E Linder, and Kendall J Blumer.
• Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
• J. Biol. Chem. 2006 Sep 22; 281 (38): 28222-31.

AbstractThe RGS7 (R7) family of G protein regulators, Gbeta5, and R7BP form heterotrimeric complexes that potently regulate the kinetics of G protein-coupled receptor signaling. Reversible palmitoylation of R7BP regulates plasma membrane/nuclear shuttling of R7*Gbeta5*R7BP heterotrimers. Here we have investigated mechanisms whereby R7BP controls the function of the R7 family. We show that unpalmitoylated R7BP undergoes nuclear/cytoplasmic shuttling and that a C-terminal polybasic motif proximal to the palmitoylation acceptor sites of R7BP mediates nuclear localization, palmitoylation, and plasma membrane targeting. These results suggest a novel mechanism whereby palmitoyltransferases and nuclear import receptors both utilize the C-terminal domain of R7BP to determine the trafficking fate of R7*Gbeta5*R7BP heterotrimers. Analogous mechanisms may regulate other signaling proteins whose distribution between the plasma membrane and nucleus is controlled by palmitoylation. Lastly, we show that cytoplasmic RGS7*Gbeta5*R7BP heterotrimers and RGS7*Gbeta5 heterodimers are equivalently inefficient regulators of G protein-coupled receptor signaling relative to plasma membrane-bound heterotrimers bearing palmitoylated R7BP. Therefore, R7BP augments the function of the complex by a palmitoylation-regulated plasma membrane-targeting mechanism.

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