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Author Notes:

Correspondence to: P.M. Iuvone, Department of Pharmacology, Emory University School of Medicine, 1510 Clifton Rd, Atlanta, Georgia, 30322; Fax: 404-727-0365; Email: miuvone@pharm.emory.edu

The authors are grateful to Amy Visser, Holly Zhou for assistance genotyping the mice, to David Grandy and Malcolm Low (Oregon Health Sciences University) for providing the Drd4−/− breeder mice, and Maxim Sokolov (West Virginia University) for providing the pSer54-Pdc antibody.

Subjects:

Research Funding:

This study was supported by NIH grants EY004864 and EY014764 (PMI), NS43459 (GT), and a VA Merit Award (RHL).

NP and SR were supported by a grant RUB1-2637 from the U.S. Civilian Research & Development Foundation.

Keywords:

  • Phosducin
  • retina
  • circadian clocks
  • dopamine D4 receptors

Dopamine modulates diurnal and circadian rhythms of protein phosphorylation in photoreceptor cells of mouse retina

Tools:

Journal Title:

European Journal of Neuroscience

Volume:

Volume 27, Number 10

Publisher:

, Pages 2691-2700

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Many aspects of photoreceptor metabolism are regulated as diurnal or circadian rhythms. The nature of the signals that drive rhythms in mouse photoreceptors is unknown. Dopamine amacrine cells in mouse retina express core circadian clock genes, leading us to test the hypothesis that dopamine regulates rhythms of protein phosphorylation in photoreceptor cells. To this end, we investigated the phosphorylation of phosducin, an abundant photoreceptor-specific phosphoprotein. In mice exposed to a daily light-dark cycle, robust daily rhythms of phosducin phosphorylation and retinal dopamine metabolism were observed. Phospho-phosducin levels were low during the daytime and high at night, and correlated negatively with levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid. The effect of light on phospho-phosducin levels was mimicked by pharmacological activation of dopamine D4 receptors. The amplitude of the diurnal rhythm of phospho-phosducin was reduced by more than 50% in D4 receptor knockout mice, due to higher daytime levels of phospho-phosducin. In addition, the daytime level of phospho-phosducin was significantly elevated by L-745,870, a dopamine D4 receptor antagonist. These data indicate that dopamine and other light-dependent processes cooperatively regulate the diurnal rhythm of phosducin phosphorylation. Under conditions of constant darkness, a circadian rhythm of phosducin phosphorylation was observed, which correlated negatively with a circadian rhythm of 3,4-dihydroxyphenylacetic acid level. The circadian fluctuation of phospho-phosducin was completely abolished by constant infusion of L-745,870, indicating that the rhythm of phospho-phosducin level is driven by dopamine. Thus, dopamine release in response to light and circadian clocks drives daily rhythms of protein phosphorylation in photoreceptor cells.

Copyright information:

© The Authors 2008. Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd

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