title: Arrestin-1 expression level in rods: balancing functional performance and photoreceptor health.
abstract: In rod photoreceptors, signaling persists as long as rhodopsin remains catalytically active. Phosphorylation by rhodopsin kinase followed by arrestin-1 binding completely deactivates rhodopsin. Timely termination prevents excessive signaling and ensures rapid recovery. Mouse rods express arrestin-1 and rhodopsin at ∼0.8:1 ratio, making arrestin-1 the second most abundant protein in the rod. The biological significance of wild type arrestin-1 expression level remains unclear. Here we investigated the effects of varying arrestin-1 expression on its intracellular distribution in dark-adapted photoreceptors, rod functional performance, recovery kinetics, and morphology. We found that rod outer segments isolated from dark-adapted animals expressing arrestin-1 at wild type or higher level contain much greater fraction of arrestin-1 than previously estimated, 15-25% of the total. The fraction of arrestin-1 residing in the outer segments (OS) in animals with low expression (4-12% of wild type) is much lower, 5-7% of the total. Only 4% of wild type arrestin-1 level in the outer segments was sufficient to maintain near-normal retinal morphology, whereas rapid recovery required at least ∼12%. Supra-physiological arrestin-1 expression improved light sensitivity and facilitated photoresponse recovery, but was detrimental for photoreceptor health, particularly in the peripheral retina. Thus, physiological level of arrestin-1 expression in rods reflects the balance between short-term functional performance of photoreceptors and their long-term health.
authors.affiliation: Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: X
authors.initials: X
authors.lastname: Song
authors.forename: S A
authors.initials: SA
authors.lastname: Vishnivetskiy
authors.forename: J
authors.initials: J
authors.lastname: Seo
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: E V
authors.initials: EV
authors.lastname: Gurevich
authors.forename: V V
authors.initials: VV
authors.lastname: Gurevich
mesh_terms: D000818:Animals; D019390:Arrestins / Q000096:biosynthesis* / Q000235:genetics; D003624:Darkness; D004596:Electroretinography; D051379:Mice; D008822:Mice, Transgenic; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D019390:Arrestins