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The R7 RGS Protein Family: Multi-Subunit Regulators of Neuronal G Protein Signaling

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Abstract

G protein-coupled receptor signaling pathways mediate the transmission of signals from the extracellular environment to the generation of cellular responses, a process that is critically important for neurons and neurotransmitter action. The ability to promptly respond to rapidly changing stimulation requires timely inactivation of G proteins, a process controlled by a family of specialized proteins known as regulators of G protein signaling (RGS). The R7 group of RGS proteins (R7 RGS) has received special attention due to their pivotal roles in the regulation of a range of crucial neuronal processes such as vision, motor control, reward behavior, and nociception in mammals. Four proteins in this group, RGS6, RGS7, RGS9, and RGS11, share a common molecular organization of three modules: (i) the catalytic RGS domain, (ii) a GGL domain that recruits Gβ5, an outlying member of the G protein beta subunit family, and (iii) a DEP/DHEX domain that mediates interactions with the membrane anchor proteins R7BP and R9AP. As heterotrimeric complexes, R7 RGS proteins not only associate with and regulate a number of G protein signaling pathway components, but have also been found to form complexes with proteins that are not traditionally associated with G protein signaling. This review summarizes our current understanding of the biology of the R7 RGS complexes including their structure/functional organization, protein–protein interactions, and physiological roles.

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Acknowledgments

We thank Mr. Perry Anderson for his help with illustrations. Studies on R7 RGS proteins in our laboratory are supported by the NIH grants EY018139 and DA 021743. Garret Anderson is a recipient of the Ruth L. Kirschstein National Research Service Award DA024944.

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Anderson, G.R., Posokhova, E. & Martemyanov, K.A. The R7 RGS Protein Family: Multi-Subunit Regulators of Neuronal G Protein Signaling. Cell Biochem Biophys 54, 33–46 (2009). https://doi.org/10.1007/s12013-009-9052-9

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