Membrane anchor R9AP potentiates GTPase-accelerating protein activity of RGS11 x Gbeta5 complex and accelerates inactivation of the mGluR6-G(o) signaling.
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 beta subunit, Gbeta(5), 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 x Gbeta(5) complex at Galpha(o). Single turnover GTPase assays reveal that R9AP co-localizes RGS11 x Gbeta(5) and Galpha(o) on the membrane and allosterically potentiates the GTPase-accelerating function of RGS11 x Gbeta(5). Reconstitution of mGluR6-Galpha(o) signaling in Xenopus oocytes indicates that RGS11 x Gbeta(5)-mediated GTPase acceleration in this system requires co-expression of R9AP. The results provide new insight into the regulation of mGluR6-Galpha(o) signaling by the RGS11 x Gbeta(5) x R9AP complex and establish R9AP as a general GTPase-accelerating protein activity regulator of R7 RGS complexes.
Masuho
Ikuo
I
Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Celver
Jeremy
J
Kovoor
Abraham
A
Martemyanov
Kirill A
KA
D000818:Animals; D002417:Cattle; D002460:Cell Line; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D018411:Spodoptera; D014981:Xenopus
D044387:GTP-Binding Protein beta Subunits; D008565:Membrane Proteins; D020710:RGS Proteins; D018094:Receptors, Metabotropic Glutamate; C113897:metabotropic glutamate receptor 6