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N. Pozdeyev, A. Visser, S. Rozov, R.H. Lee, P.M. Iuvone; Dopamine Regulates Phosducin Ser–73 Phosphorylation in Mouse Retina . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3738.
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Phosducin is a 28–kDa phosphoprotein expressed at high levels in photoreceptor cells. Phosducin harbors a consensus phosphorylation site for cAMP–dependent protein kinase (PKA) at Ser–73. Phosducin is phosphorylated and complexed with 14–3–3 proteins in dark adapted photoreceptors. In response to light, phosducin is dephosphorylated, released from the complex with 14–3–3 proteins, and binds to G protein ßγ subunits, which regulate signal transduction within photoreceptors. Photoreceptor cells express dopamine D4 receptors coupled to cAMP metabolism. We hypothesize that dopamine may regulate phosducin function by binding to D4 receptors and inhibiting cAMP dependent Ser–73 phosphorylation by PKA.
Experiments were performed on wild type and dopamine D4 receptor knock–out mice on a C57Bl/6J background. Immunoblotting with phosphospecific (pSer–73) and pan–phosducin antibodies was used to quantify pSer–73 and total phosducin. Quinpirole, a dopamine D2/D4 receptor agonist, was injected intraperitoneally at doses 0.01–3 mg/kg of body weight.
Quinpirole dose–dependently decreased pSer–73 of phosducin in retinas of dark–adapted wild type mice, mimicking the effect of light; quinpirole had no effect on the total phosducin concentration. Quinpirole did not affect phosducin phosphorylation in retinas of D4 knock–out mice. Exposure of dark–adapted wild type animals to 60 min of light caused ∼83% reduction in pSer–73 phosducin. In contrast, light exposure under these conditions decreased pSer–73 phosducin in D4 receptor knock–out mice by only ∼20%. During the daytime, when the retinal dopamine concentration is high, the amount of pSer–73 phosducin was significantly higher in D4 knock–out mice when compared to wild type controls.
These data indicate that activation of dopamine D4 receptors decreases phosducin Ser–73 phosphorylation in photoreceptor cells. We suggest that the regulation of phosducin function by dopamine may serve as a mechanism regulating diurnal changes in signaling in photoreceptor cells.
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