Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation (original) (raw)

Nature volume 427, pages 75–78 (2004)Cite this article

Abstract

The RGS proteins are GTPase activating proteins that accelerate the deactivation of G proteins in a variety of signalling pathways in eukaryotes1,2,3,4,5,6. RGS9 deactivates the G proteins (transducins) in the rod and cone phototransduction cascades7,8. It is anchored to photoreceptor membranes by the transmembrane protein R9AP (RGS9 anchor protein), which enhances RGS9 activity up to 70-fold9,10,11. If RGS9 is absent or unable to interact with R9AP, there is a substantial delay in the recovery from light responses in mice4,12,13. 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.

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Acknowledgements

We thank T. Li, T. McGee and B. Pawlyk for assistance. This study followed the tenets of the Declaration of Helsinki; it was approved by the Human Studies Committees of the authors' institutions and all patients gave their consent before their participation. This work was supported by the NIH, the Foundation Fighting Blindness, Owings Mills, Maryland, and the American Heart Association.

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Author notes

  1. Stephanie A. Hagstrom
    Present address: Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio, 44195, USA

Authors and Affiliations

  1. Ocular Molecular Genetics Institute, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, 02114, USA
    Koji M. Nishiguchi, Stephanie A. Hagstrom & Thaddeus P. Dryja
  2. Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, 02114, USA
    Michael A. Sandberg & Eliot L. Berson
  3. Howe Laboratory of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, 02114, USA
    Kirill A. Martemyanov & Vadim Y. Arshavsky
  4. Department of Ophthalmology, University Hospital Groningen, Groningen, 9700 RB, The Netherlands
    Aart C. Kooijman & Jan W. R. Pott

Authors

  1. Koji M. Nishiguchi
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  2. Michael A. Sandberg
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  3. Aart C. Kooijman
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  4. Kirill A. Martemyanov
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  5. Jan W. R. Pott
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  6. Stephanie A. Hagstrom
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  7. Vadim Y. Arshavsky
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  8. Eliot L. Berson
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  9. Thaddeus P. Dryja
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Correspondence toThaddeus P. Dryja.

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Nishiguchi, K., Sandberg, M., Kooijman, A. et al. Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation.Nature 427, 75–78 (2004). https://doi.org/10.1038/nature02170

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