title: Gbeta5-RGS complexes co-localize with mGluR6 in retinal ON-bipolar cells.
abstract: The time course of G-protein-coupled responses is largely determined by the kinetics of GTP hydrolysis by the G protein alpha subunit, which is accelerated by interaction with regulator of G-protein signaling (RGS) proteins. Light responses of ON-bipolar cells of the vertebrate retina require rapid inactivation of the G protein Galphao, which is activated in the dark by metabotropic glutamate receptor, mGluR6, in their dendritic tips. It is not yet known, however, which RGS protein(s) might be responsible for rapid inactivation kinetics. By immunofluorescence and co-immunoprecipitation, we have identified complexes of the Galphao-selective RGS proteins RGS7 and RGS11, with their obligate binding partner, Gbeta5, that are localized to the dendritic tips of murine rod and cone ON-bipolar cells, along with mGluR6. Experiments using pre- and post-synaptic markers, and a dissociated bipolar cell preparation, clearly identified the location of these complexes as the ON-bipolar cell dendritic tips and not the adjacent photoreceptor terminals or horizontal cell dendrites. In mice lacking mGluR6, the distribution of RGS11, RGS7 and Gbeta5 shifts away from the dendritic tips, implying a functional relationship with mGluR6. The precise co-localization of Gbeta5-RGS7 and Gbeta5-RGS11 with mGluR6, and the dependence of localization on the presence of mGluR6, suggests that Gbeta5-RGS7 and Gbeta5-RGS11 function specifically in the mGluR6 signal transduction pathway, where they may stimulate the GTPase activity of Galphao, thus accelerating the ON-bipolar cell light response, in a manner analogous to the acceleration of photoreceptor light responses by the Gbeta5-RGS9-1 complex.
authors.affiliation: Neurological Sciences Institute, Oregon Health and Science University, Beaverton, OR 97006, USA. morgansc@ohsu.edu
authors.forename: Catherine W
authors.initials: CW
authors.lastname: Morgans
authors.forename: Theodore G
authors.initials: TG
authors.lastname: Wensel
authors.forename: R Lane
authors.initials: RL
authors.lastname: Brown
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Perez-Leon
authors.forename: Ben
authors.initials: B
authors.lastname: Bearnot
authors.forename: Robert M
authors.initials: RM
authors.lastname: Duvoisin
mesh_terms: D000818:Animals; D020555:GTP-Binding Protein Regulators / Q000378:metabolism*; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism*; D047468:Immunoprecipitation / Q000379:methods; D051379:Mice; D051571:Protein Kinase C-alpha / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012160:Retina / Q000166:cytology*; D051245:Retinal Bipolar Cells / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D020555:GTP-Binding Protein Regulators; D044387:GTP-Binding Protein beta Subunits; D018094:Receptors, Metabotropic Glutamate; C113897:metabotropic glutamate receptor 6; D051571:Protein Kinase C-alpha