![]() ![]() This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: The authors confirm that all data underlying the findings are fully available without restriction. Received: MaAccepted: JPublished: August 14, 2014Ĭopyright: © 2014 Lee et al. PLoS Genet 10(8):Įditor: Choogon Lee, Florida State University, United States of America (2014) Phosphorylation of a Central Clock Transcription Factor Is Required for Thermal but Not Photic Entrainment. Our findings suggest a novel role for clock protein phosphorylation in governing the effective strengths of entraining modalities by adjusting clock amplitude.Ĭitation: Lee E, Jeong EH, Jeong H-J, Yildirim E, Vanselow JT, Ng F, et al. Surprisingly, the clock-controlled daily activity rhythm fails to maintain synchrony with daily temperature cycles, although there is no observable defect in aligning to light/dark cycles. Blocking global phosphorylation of dCLOCK by mutating phospho-acceptor sites to alanine increases its abundance and transcriptional activity, leading to higher peak values and amplitudes in the mRNA rhythms of core clock genes, which likely explains the accelerated clock speed. Using mass-spectrometry, we identified more than a dozen phosphorylation sites on dCLOCK. However, the role of CLOCK phosphorylation at the organismal level is still unclear. dCLOCK undergoes temporal changes in phosphorylation throughout a day, which is also observed for mammalian CLOCK. In Drosophila, dCLOCK is a master circadian transcription factor that drives cyclical gene expression and is likely the rate-limiting component in the transcriptional/translational feedback loops that underlie the timekeeping mechanism. Although light is generally thought to be the most dominant entraining cue in nature, daily cycles in temperature are sufficient to synchronize clocks in a large range of organisms. Our findings suggest a novel role for clock protein phosphorylation in governing the relative strengths of entraining modalities by adjusting the dynamics of circadian gene expression.Ĭircadian clocks are synchronized to local time by daily cycles in light-dark and temperature. Surprisingly, the clock-controlled daily activity rhythm in dCLK-15A expressing flies does not synchronize properly to daily temperature cycles, although there is no defect in aligning to light/dark cycles. The dCLK-15A protein attains substantially higher levels in flies compared to the control situation, and also appears to have enhanced transcriptional activity, consistent with the observed higher peak values and amplitudes in the mRNA rhythms of several core clock genes. Expression of a mutated version of dCLK where all the mapped phospho-sites were switched to alanine (dCLK-15A) rescues the arrythmicity of Clk out flies, yet with an approximately 1.5 hr shorter period. Using a Drosophila tissue culture system, we identified multiple phosphorylation sites on dCLK. However, the physiological role of dCLK phosphorylation is not clear. ![]() ![]() dCLOCK (dCLK), the master transcription factor driving cyclical gene expression and the rate-limiting component in the Drosophila circadian clock, undergoes daily changes in phosphorylation. Moreover, phosphorylation of clock proteins plays crucial roles in the temporal regulation of clock protein activity, stability and subcellular localization. Transcriptional/translational feedback loops drive daily cycles of expression in clock genes and clock-controlled genes, which ultimately underlie many of the overt circadian rhythms manifested by organisms.
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