Sleep Health | Sleep Review
A recent discovery from Northwestern University published in the Proceedings of the National Academy of Sciences (PNAS) could help understand how the circadian clock is linked to genetics. A team of neurobiologists identified a new gene called Tango10, which is crucial for daily behavior. This gene is involved in a molecular pathway by which the circadian clock (the “gears”) controls the cellular output of the clock (the “hands”) to guide the daily sleep-wake cycles.
While the study was conducted on the Drosophila melanogaster fruit fly, the results have implications for humans. Knowing how this signaling pathway works could lead to therapeutics for the relief of sleep problems and could provide information about clock-related human diseases such as depression, neurodegenerative diseases and metabolic diseases.
“Scientists know a lot about the clock’s ‘gears’ but not so much about the ‘hands’ where the behavior is generated or the connection between the two,” says Ravi Allada, MD, a chronobiologist who led the study. in a press release.
“We wanted to better understand the molecular basis of the daily ‘wake-up signal’ that alerts an animal that it is time to wake up,” he said. “In this study, we focused on pacemaker neurons that control the sleep-wake cycle and used genetic screenings to identify genes that regulate the neurons.”
Allada is the Edgar C. Stuntz Distinguished Professor of Neuroscience and Chair of the Neurobiology Department at Weinberg College of Arts and Sciences. Allada is also the associate director of the Northwestern Center for Sleep and Circadian Biology.
In addition to the flying experiments performed in Allada’s laboratory, the Northwestern team worked with Casey Diekman and Matthew Moyeat of the New Jersey Institute of Technology, who performed computer modeling experiments.
The northwest researchers examined a number of genes that they thought might be important in the functioning of the circadian clock and the behavior of the fly. It was through this process that they discovered the gene called Tango10. When this gene was switched off, the fly lost its normal 24-hour behavioral rhythm. Certain currents of potassium were reduced, likely leading to hyperactive neurons and contributing to a loss of regular rhythm.
Under normal conditions in the fly, Tango10 protein levels rise and fall with circadian time, which can modulate the activity of neurons to go up and down, which in turn can drive the animal’s sleep-wake cycle and behavior. In flies that lack the Tango10 gene, this circadian rhythm is disrupted.
“Our results close a molecular gap in our understanding of how the clock’s core wheels control the hands,” said Allada.
The title of the article is: “The E3 ubiquitin ligase adapter Tango10 connects the central circadian clock with neuropeptides and behavioral rhythms”. The co-first authors are Jongbin Lee and Chunghun Lim, former postdocs in Allada’s laboratory.
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