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R9AP stabilizes RGS11-Gβ5 and accelerates the early light response of ON-bipolar cells

Published online by Cambridge University Press:  26 January 2010

BRETT G. JEFFREY*
Affiliation:
Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
CATHERINE W. MORGANS
Affiliation:
Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
THERESA PUTHUSSERY
Affiliation:
Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
THEODORE G. WENSEL
Affiliation:
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas
NEAL S. BURKE
Affiliation:
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, Washington
R. LANE BROWN
Affiliation:
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, Washington
ROBERT M. DUVOISIN
Affiliation:
Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, Oregon
*
*Address correspondence and reprint requests to: Brett G. Jeffrey, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006. E-mail: jeffreyb@ohsu.edu

Abstract

The rate-limiting step in the recovery of the photoreceptor light response is the hydrolysis of GTP by transducin, a reaction that is accelerated by the RGS9–Gβ5 complex, and its membrane anchor, R9AP. Similar complexes, including RGS7, RGS11, and Gβ5, are found in retinal ON-bipolar cell dendrites. Here, we present evidence that R9AP is also expressed in the dendritic tips of ON-bipolar cells. Immunofluorescent staining for R9AP revealed a punctate pattern of labeling in the outer plexiform layer, where it colocalized with mGluR6. In photoreceptors, R9AP is required for proteolytic stability of the entire regulator of G protein signaling complex, and we found that genetic deletion of R9AP also results in a marked reduction in the levels of RGS11 and Gβ5 in the bipolar cell dendrites; the level of RGS7 was unaffected, suggesting the presence of another interaction partner to stabilize RGS7. To determine the effect of R9AP deletion on the response kinetics of ON-bipolar cells, we compared the electroretinogram (ERG) between wild-type and R9AP-deficient mice. The ERG b-wave, reflecting ON-bipolar cell activity, was delayed and larger in the R9AP-deficient mice. Our data indicate that R9AP is required for stable expression of RGS11–Gβ5 in ON-bipolar cell dendrites. Furthermore, they suggest that the RGS11–Gβ5–R9AP complex accelerates the initial ON-bipolar cell response to light.

Type
Research Articles
Copyright
Copyright © Cambridge University Press 2010

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