R7BP augments the function of RGS7*Gbeta5 complexes by a plasma membrane-targeting mechanism.

The 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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Cell Line, Cell Membrane, Cell Nucleus, Cytoplasm, G Protein-Coupled Inwardly-Rectifying Potassium Channels, GTP-Binding Protein beta Subunits, Humans, Membrane Proteins, Nerve Tissue Proteins, Nuclear Localization Signals, Palmitic Acid, Phospholipid Transfer Proteins, Protein Transport, RGS Proteins, Receptors, G-Protein-Coupled, Signal Transduction, Xenopus laevis
J. Biol. Chem.
Date: Sep. 22, 2006
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