Rhodopsin kinase activity modulates the amplitude of the visual response in Drosophila

doi:10.1073/pnas.0402205101

Rhodopsin kinase activity modulates the amplitude of the visual response in Drosophila

Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205

Edited by Robert J. Lefkowitz, Duke University Medical Center, Durham, NC (received for review March 29, 2004)

Abstract

A feature shared between Drosophila rhodopsin and nearly all other G protein-coupled receptors is agonist-dependent protein phosphorylation. Despite extensive analyses of Drosophila phototransduction, the identity and function of the rhodopsin kinase (RK) have been elusive. Here, we provide evidence that G protein-coupled receptor kinase 1 (GPRK1), which is most similar to the β-adrenergic receptor kinases, G protein-coupled receptor kinase 2 (GRK2) and GRK3, is the fly RK. We show that GPRK1 is enriched in photoreceptor cells, associates with the major Drosophila rhodopsin, Rh1, and phosphorylates the receptor. As is the case with mammalian GRK2 and GRK3, Drosophila GPRK1 includes a C-terminal pleckstrin homology domain, which binds to phosphoinositides and the Gβγ subunit. To address the role of GPRK1, we generated transgenic flies that expressed higher and lower levels of RK activity. Those flies with depressed levels of RK activity displayed a light response with a much larger amplitude than WT. Conversely, the amplitude of the light response was greatly suppressed in transgenic flies expressing abnormally high levels of RK activity. These data point to an evolutionarily conserved role for GPRK1 in modulating the amplitude of the visual response.

Footnotes

↵ † To whom correspondence should be addressed. E-mail: cmontell{at}jhmi.edu.
↵ * Present address: Department of Biochemistry and Biophysics, Mission Bay Genetech Hall, University of California, San Francisco, CA 94143.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: PH, pleckstrin homology; GRK (or GPRK), G protein-coupled receptor kinase; PI, phosphoinositide; RK, rhodopsin kinase; IP, immunoprecipitation; ERG, electroretinogram; TRP, transient receptor potential.