Membrane Anchor R9AP Potentiates GTPase-accelerating Protein Activity of RGS11·Gβ₅ Complex and Accelerates Inactivation of the mGluR6-G₀ Signaling

Authors

Ikuro Masuho
Jeremy Celver, University of Rhode Island
Abraham Kovoor, University of Rhode IslandFollow
Kirill A. Martemyanov

Document Type

Article

Date of Original Version

2010

Department

Biomedical and Pharmaceutical Sciences

Abstract

The R7 subfamily of RGS proteins critically regulates neuronal G protein-signaling pathways that are essential for vision, nociception, motor coordination, and reward processing. A member of the R7 RGS family, RGS11, is a GTPase-accelerating protein specifically expressed in retinal ON-bipolar cells where it forms complexes with the atypical G protein β subunit, Gβ₅, and transmembrane protein R9AP. Association with R9AP has been shown to be critical for the proteolytic stability of the complex in the retina. In this study we report that R9AP can in addition stimulate the GTPase-accelerating protein activity of the RGS11·Gβ₅ complex at Gα_o. Single turnover GTPase assays reveal that R9AP co-localizes RGS11·Gβ₅ and Gα_o on the membrane and allosterically potentiates the GTPase-accelerating function of RGS11·Gβ₅. Reconstitution of mGluR6-Gα_o signaling in Xenopus oocytes indicates that RGS11·Gβ₅-mediated GTPase acceleration in this system requires co-expression of R9AP. The results provide new insight into the regulation of mGluR6-Gα_o signaling by the RGS11·Gβ₅·R9AP complex and establish R9AP as a general GTPase-accelerating protein activity regulator of R7 RGS complexes.

Citation/Publisher Attribution

Masuho, I., Celver, J., Kovoor, A., & Martemyanov, K. A. (2010). Membrane Anchor R9AP Potentiates GTPase-accelerating Protein Activity of RGS11·Gβ₅ Complex and Accelerates Inactivation of the mGluR6-G₀ Signaling. Journal of Biological Chemistry, 285, 4781-4787. doi: 10.1074/jbc.M109.058511

Available at: http://dx.doi.org/10.1074/jbc.M109.058511