Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Nishiguchi, KM; Sandberg, MA; Kooijman, AC; Martemyanov, KA; Pott, JWR; Hagstrom, SA; Arshavsky, VY; Berson, EL; Dryja, TP

Published Date

  • January 1, 2004

Published In

Volume / Issue

  • 427 / 6969

Start / End Page

  • 75 - 78

PubMed ID

  • 14702087

Pubmed Central ID

  • 14702087

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/nature02170

Language

  • eng

Conference Location

  • England