title: Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation.
abstract: The RGS proteins are GTPase activating proteins that accelerate the deactivation of G proteins in a variety of signalling pathways in eukaryotes. RGS9 deactivates the G proteins (transducins) in the rod and cone phototransduction cascades. It is anchored to photoreceptor membranes by the transmembrane protein R9AP (RGS9 anchor protein), which enhances RGS9 activity up to 70-fold. If RGS9 is absent or unable to interact with R9AP, there is a substantial delay in the recovery from light responses in mice. We identified five unrelated patients with recessive mutations in the genes encoding either RGS9 or R9AP who reported difficulty adapting to sudden changes in luminance levels mediated by cones. Standard visual acuity was normal to moderately subnormal, but the ability to see moving objects, especially with low-contrast, was severely reduced despite full visual fields; we have termed this condition bradyopsia. To our knowledge, these patients represent the first identified humans with a phenotype associated with reduced RGS activity in any organ.
authors.affiliation: Ocular Molecular Genetics Institute, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, USA.
authors.forename: Koji M
authors.initials: KM
authors.lastname: Nishiguchi
authors.forename: Michael A
authors.initials: MA
authors.lastname: Sandberg
authors.forename: Aart C
authors.initials: AC
authors.lastname: Kooijman
authors.forename: Kirill A
authors.initials: KA
authors.lastname: Martemyanov
authors.forename: Jan W R
authors.initials: JW
authors.lastname: Pott
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Hagstrom
authors.forename: Vadim Y
authors.initials: VY
authors.lastname: Arshavsky
authors.forename: Eliot L
authors.initials: EL
authors.lastname: Berson
authors.forename: Thaddeus P
authors.initials: TP
authors.lastname: Dryja
mesh_terms: D000222:Adaptation, Physiological / Q000528:radiation effects; D048868:Adaptor Proteins, Signal Transducing; D020134:Catalytic Domain; D005808:Genes, Recessive; D006801:Humans; D008027:Light; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*; D011487:Protein Conformation; D020710:RGS Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014786:Vision Disorders / Q000235:genetics* / Q000503:physiopathology*; D014785:Vision, Ocular / Q000502:physiology* / Q000528:radiation effects; D014792:Visual Acuity / Q000502:physiology / Q000528:radiation effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D020710:RGS Proteins; C464657:RGS9BP protein, human; C116925:regulator of g-protein signaling 9