RGS expression rate-limits recovery of rod photoresponses.
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.
Krispel
Claudia M
CM
Center for Neuroscience, University of California, Davis, 95616, USA.
Chen
Desheng
D
Melling
Nathan
N
Chen
Yu-Jiun
YJ
Martemyanov
Kirill A
KA
Quillinan
Nidia
N
Arshavsky
Vadim Y
VY
Wensel
Theodore G
TG
Chen
Ching-Kang
CK
Burns
Marie E
ME
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
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