title: Rhodopsin kinase and arrestin binding control the decay of photoactivated rhodopsin and dark adaptation of mouse rods.
abstract: Photoactivation of vertebrate rhodopsin converts it to the physiologically active Meta II (R*) state, which triggers the rod light response. Meta II is rapidly inactivated by the phosphorylation of C-terminal serine and threonine residues by G-protein receptor kinase (Grk1) and subsequent binding of arrestin 1 (Arr1). Meta II exists in equilibrium with the more stable inactive form of rhodopsin, Meta III. Dark adaptation of rods requires the complete thermal decay of Meta II/Meta III into opsin and all-trans retinal and the subsequent regeneration of rhodopsin with 11-cis retinal chromophore. In this study, we examine the regulation of Meta III decay by Grk1 and Arr1 in intact mouse rods and their effect on rod dark adaptation. We measure the rates of Meta III decay in isolated retinas of wild-type (WT), Grk1-deficient (Grk1(-/-)), Arr1-deficient (Arr1(-/-)), and Arr1-overexpressing (Arr1(ox)) mice. We find that in WT mouse rods, Meta III peaks ∼6 min after rhodopsin activation and decays with a time constant (τ) of 17 min. Meta III decay slows in Arr1(-/-) rods (τ of ∼27 min), whereas it accelerates in Arr1(ox) rods (τ of ∼8 min) and Grk1(-/-) rods (τ of ∼13 min). In all cases, regeneration of rhodopsin with exogenous 11-cis retinal is rate limited by the decay of Meta III. Notably, the kinetics of rod dark adaptation in vivo is also modulated by the levels of Arr1 and Grk1. We conclude that, in addition to their well-established roles in Meta II inactivation, Grk1 and Arr1 can modulate the kinetics of Meta III decay and rod dark adaptation in vivo.
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118 rikardf@bu.edu.
authors.forename: Rikard
authors.initials: R
authors.lastname: Frederiksen
authors.affiliation: Department of Electronics and Communications Engineering, BioMediTech, Tampere University of Technology, 33720 Tampere, Finland.
authors.forename: Soile
authors.initials: S
authors.lastname: Nymark
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kolesnikov
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Berry
authors.affiliation: Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425.
authors.forename: Leopold
authors.initials: L
authors.lastname: Adler
authors.affiliation: Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425.
authors.forename: Yiannis
authors.initials: Y
authors.lastname: Koutalos
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Vladimir J
authors.initials: VJ
authors.lastname: Kefalov
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118.
authors.forename: M Carter
authors.initials: MC
authors.lastname: Cornwall
mesh_terms: D000818:Animals; D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D003623:Dark Adaptation / Q000502:physiology*; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D010775:Photic Stimulation; D011485:Protein Binding; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D012243:Rhodopsin / Q000378:metabolism
chemical_list: D019390:Arrestins; C000607302:arrestin 1 protein, mouse; D012243:Rhodopsin; D051606:G-Protein-Coupled Receptor Kinase 1; C496762:Grk1 protein, mouse