Arrestin competition influences the kinetics and variability of the single-photon responses of mammalian rod photoreceptors.
Reliable signal transduction via G-protein-coupled receptors requires proper receptor inactivation. For example, signals originating from single rhodopsin molecules vary little from one to the next, requiring reproducible inactivation of rhodopsin by phosphorylation and arrestin binding. We determined how reduced concentrations of rhodopsin kinase (GRK1) and/or arrestin1 influenced the kinetics and variability of the single-photon responses of mouse rod photoreceptors. These experiments revealed that arrestin, in addition to its role in quenching the activity of rhodopsin, can tune the kinetics of rhodopsin phosphorylation by competing with GRK1. This competition influenced the variability of the active lifetime of rhodopsin. Biasing the competition in favor of GRK1 revealed that rhodopsin remained active through much of the single-photon response under the conditions of our experiments. This long-lasting rhodopsin activity can explain the characteristic time course of single-photon response variability. Indeed, explaining the late time-to-peak of the variance required an active lifetime of rhodopsin approximately twice that of the G-protein transducin. Competition between arrestins and kinases may be a general means of influencing signals mediated by G-protein-coupled receptors, particularly when activation of a few receptors produces signals of functional importance.
Doan
Thuy
T
University of Washington, Seattle, 98195, USA.
Azevedo
Anthony W
AW
Hurley
James B
JB
Rieke
Fred
F
D000818:Animals; D019393:Arrestin / Q000235:genetics / Q000378:metabolism*; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000378:metabolism*; D007700:Kinetics; D008390:Markov Chains; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008959:Models, Neurological; D010766:Phosphorylation; D010775:Photic Stimulation; D017785:Photons; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D012243:Rhodopsin / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors
D019393:Arrestin; D012243:Rhodopsin; D051606:G-Protein-Coupled Receptor Kinase 1; C496762:Grk1 protein, mouse