title: Photoreceptor pathology in the X-linked retinoschisis (XLRS) mouse results in delayed rod maturation and impaired light driven transducin translocation.
abstract: Light-activated movement of transducin-α (Gαt1) from rod photoreceptor outer segments (ROS) into inner segments (IS) enables rods to rapidly adapt to changes in light intensity. The threshold light intensity at which Gαt1 translocates from ROS into IS is primarily determined by the rates of activation and inactivation of Gαt1. Loss- of- expression of the retina specific cell surface protein, retinoschsin (Rs1-KO), led to a dramatic 3-10 fold increase, depending on age, in the luminance threshold for transducin translocation from ROS into IS compared with wild-type control. In contrast, arrestin translocated from IS into ROS at the same light intensity both in WT and Rs1-KO mice. Biochemical changes, including reduced transducin protein levels and enhanced transducin GTPase activity, explain the shift in light intensity threshold for Gαt1 translocation in Rs1-KO mice. These changes in Rs1-KO mice were also associated with age related alterations in photoreceptor morphology and transcription factor expression that suggest delayed photoreceptor maturation.
authors.affiliation: G. B. Bietti Foundation, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00198, Rome, Italy, luxzic@hotmail.com.
authors.forename: Lucia
authors.initials: L
authors.lastname: Ziccardi
authors.forename: Camasamudram
authors.initials: C
authors.lastname: Vijayasarathy
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Bush
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sieving
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism*; D006801:Humans; D008027:Light; D051379:Mice; D018345:Mice, Knockout; D055211:Retinal Photoreceptor Cell Inner Segment / Q000378:metabolism / Q000473:pathology; D055214:Retinal Photoreceptor Cell Outer Segment / Q000378:metabolism / Q000473:pathology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D041441:Retinoschisis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015293:Transducin / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D005136:Eye Proteins; D044385:GTP-Binding Protein alpha Subunits; C488949:Gnat1 protein, mouse; C491843:RS1 protein, mouse; D015293:Transducin