UC DAVIS (US) — Fooling fruit flies into thinking the day is 16 hours long instead of 24 could help alleviate human sleep disorders.
Mutating one amino acid in a single protein, slows down or speeds up the circadian clock of Drosophila melanogaster, the common fruit fly.
“Our goal, of course, is not to trick flies into thinking the day is shorter or longer, but to dissect this complex phospho-circuit (phosphorylation sites) that controls clock speed in metazoans,” says Joanna Chiu, assistant professor of entomology at the University of California, Davis.
The research is published in the journal Cell.
In previous studies, researchers identified at least 30 phosphorylation sites on a fly protein, Period, that exist in all insects and mammals and is involved in the regulation of circadian rhythms.
“We know that besides affecting degradation rate, phosphorylation of Period, proteins also affects its subcellular localization and transcriptional repressor function,” Chiu says.
The research also shows that the protein kinase Nemo is involved in animal clockworks, a protein never linked before to the regulation of circadian rhythms.
Specifically, researchers identified a cluster of Period phosphorylation sites including serine 596, whose function is to delay the phosphorylation of serine 47, an event that promotes Period degradation. Phosphorylation of serine 596 therefore indirectly slows down the degradation rate of Period.
Abnormal Period phosphorylation has been linked to human sleep disorders. This is the first phospho-delay circuitry ever identified in organismal clocks.
“Living organisms—plants, animals and even bacteria—have an internal clock or timer that helps them to determine the time of day,” Chiu says.
“This internal clock is vital to their survival since it allows them to synchronize their activity to the natural environment, so that they can perform necessary tasks at biologically advantageous times of day.
“A functional clock is required to generate proper circadian rhythms of physiology and behavior including the sleep-wake cycle, daily hormonal variations and mating rhythms,” she says.
“Based on genetics, molecular biology and biochemical experiments performed in many different model organisms, we know that the speed of the internal clock is controlled by a core set of circadian proteins,” Chiu explains.
“In insects as well as in mammals, the daily changes in Period protein levels represent a key variable in determining clock speed. De novo synthesis of Period begins around mid-morning.
“Levels of Period proteins continue to build up throughout the day and into the night, until they are “tagged” for degradation in the early morning hours. This biochemical cycle of the Period proteins intelligently corresponds to duration of a day,” she says.
“If for any reason the timing of the biochemical cycle of Period is altered, the speed of our internal clock will be different.”
Researchers from Rutgers contributed to the study that was funded by National Institutes of Health.
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