title: Exchange of Cone for Rod Phosphodiesterase 6 Catalytic Subunits in Rod Photoreceptors Mimics in Part Features of Light Adaptation.
abstract: Despite the expression of homologous phototransduction components, the molecular basis for differences in light-evoked responses between rod and cone photoreceptors remains unclear. We examined the role of cGMP phosphodiesterase (PDE6) in this difference by expressing cone PDE6 (PDE6C) in rd1/rd1 rods lacking rod PDE6 (PDE6AB) using transgenic mice. The expression of PDE6C rescues retinal degeneration observed in rd1/rd1 rods. Double-transgenic rods (PDE6C++) were compared with rd1/+ rods based on similar PDE6 expression. PDE6C increased the basal PDE activity and speeded the rate-limiting step for phototransduction deactivation, causing rod photoresponses to appear light adapted, with reduced dark current and sensitivity and faster response kinetics. When PDE6C++ and rd1/+ rods were exposed to similar background light, rd1/+ rods displayed greater desensitization. These results indicate an increased spontaneous activity and faster deactivation of PDE6C compared with PDE6AB in darkness, but that background light increases steady PDE6C activity to a lesser extent. In addition to accelerating the recovery of the photoresponse, faster PDE6C deactivation may blunt the rise in background-induced steady PDE6C activity. Therefore, higher basal PDE6C activity and faster deactivation together partially account for faster and less sensitive cone photoresponses in darkness, whereas a reduced rise of steady PDE6C activity in background light may allow cones to avoid saturation.
  
  
  CONCLUSIONS
  Cones are the primary photoreceptors responsible for most of our visual experience. Cone light responses are less sensitive and display speeded responses compared with rods. Despite the fact that rods and cones use a G-protein signaling cascade with similar organization, the mechanistic basis for these differences remains unclear. Here, we examined the role of distinct isoforms of PDE6, the effector enzyme in phototransduction, in these differences. We developed a transgenic mouse model that expresses cone PDE6 in rods and show that the cone PDE6 isoform is partially responsible for the difference in sensitivity and response kinetics between rods and cones.
authors.affiliation: Department of Molecular Physiology and Biophysics and.
authors.forename: Anurima
authors.initials: A
authors.lastname: Majumder
authors.affiliation: Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, California 90095.
authors.forename: Johan
authors.identifier: http://orcid.org/0000-0002-4038-9693
authors.initials: J
authors.lastname: Pahlberg
authors.affiliation: Department of Molecular Physiology and Biophysics and.
authors.forename: Hakim
authors.initials: H
authors.lastname: Muradov
authors.affiliation: Department of Molecular Physiology and Biophysics and.
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Boyd
authors.affiliation: Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, California 90095 nikolai-artemyev@uiowa.edu asampath@jsei.ucla.edu.
authors.forename: Alapakkam P
authors.initials: AP
authors.lastname: Sampath
authors.affiliation: Department of Molecular Physiology and Biophysics and Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa 52242, and nikolai-artemyev@uiowa.edu asampath@jsei.ucla.edu.
authors.forename: Nikolai O
authors.initials: NO
authors.lastname: Artemyev
mesh_terms: D000221:Adaptation, Ocular / Q000502:physiology*; D000818:Animals; D020134:Catalytic Domain / Q000502:physiology*; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000096:biosynthesis* / Q000235:genetics*; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*
chemical_list: D005136:Eye Proteins; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C096885:PDE6C protein, human
keywords: PDE6; cones; phototransduction; retina; rods