title: RGS expression rate-limits recovery of rod photoresponses.
abstract: Signaling through G protein-coupled receptors (GPCRs) underlies many cellular processes, yet it is not known which molecules determine the duration of signaling in intact cells. Two candidates are G protein-coupled receptor kinases (GRKs) and Regulators of G protein signaling (RGSs), deactivation enzymes for GPCRs and G proteins, respectively. Here we investigate whether GRK or RGS governs the overall rate of recovery of the light response in mammalian rod photoreceptors, a model system for studying GPCR signaling. We show that overexpression of rhodopsin kinase (GRK1) increases phosphorylation of the GPCR rhodopsin but has no effect on photoresponse recovery. In contrast, overexpression of the photoreceptor RGS complex (RGS9-1.Gbeta5L.R9AP) dramatically accelerates response recovery. Our results show that G protein deactivation is normally at least 2.5 times slower than rhodopsin deactivation, resolving a long-standing controversy concerning the mechanism underlying the recovery of rod visual transduction.
authors.affiliation: Center for Neuroscience, University of California, Davis, 95616, USA.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Krispel
authors.forename: Desheng
authors.initials: D
authors.lastname: Chen
authors.forename: Nathan
authors.initials: N
authors.lastname: Melling
authors.forename: Yu-Jiun
authors.initials: YJ
authors.lastname: Chen
authors.forename: Kirill A
authors.initials: KA
authors.lastname: Martemyanov
authors.forename: Nidia
authors.initials: N
authors.lastname: Quillinan
authors.forename: Vadim Y
authors.initials: VY
authors.lastname: Arshavsky
authors.forename: Theodore G
authors.initials: TG
authors.lastname: Wensel
authors.forename: Ching-Kang
authors.initials: CK
authors.lastname: Chen
authors.forename: Marie E
authors.initials: ME
authors.lastname: Burns
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000235:genetics / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology* / Q000528:radiation effects; D066298:In Vitro Techniques; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation / Q000528:radiation effects; D010775:Photic Stimulation / Q000379:methods; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D020127:Recovery of Function / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000166:cytology; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D013997:Time Factors; D014785:Vision, Ocular / Q000502:physiology
chemical_list: D044387:GTP-Binding Protein beta Subunits; C094668:Gnb5 protein, mouse; D020710:RGS Proteins; C116925:regulator of g-protein signaling 9; D051606:G-Protein-Coupled Receptor Kinase 1; C496762:Grk1 protein, mouse