Dopamine modulates diurnal and circadian rhythms of protein phosphorylation in photoreceptor cells of mouse retina.
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 > 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 the circadian rhythm of 3,4-dihydroxyphenylacetic acid levels. 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.
Pozdeyev
Nikita
N
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA, USA.
Tosini
Gianluca
G
Li
Li
L
Ali
Fatima
F
Rozov
Stanislav
S
Lee
Rehwa H
RH
Iuvone
P Michael
PM
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D003623:Dark Adaptation / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005136:Eye Proteins / Q000378:metabolism*; D020555:GTP-Binding Protein Regulators / Q000378:metabolism*; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010775:Photic Stimulation; D010786:Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D050638:Receptors, Dopamine D4 / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D012160:Retina / Q000166:cytology / Q000378:metabolism*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D005136:Eye Proteins; D020555:GTP-Binding Protein Regulators; D010750:Phosphoproteins; C065631:phosducin; D015102:3,4-Dihydroxyphenylacetic Acid; D050638:Receptors, Dopamine D4; D004298:Dopamine