how a specific protein regulates our circadian rhythms

The key to regulating our biological clock? A team of scientists has just discovered how a specific protein, called Casein Kinase 1 delta or CK1δ, plays a central role in the control of circadian rhythms, these natural 24-hour cycles that regulate, among other things, our phases of sleep and sleep. awakening. Published in the journal PNAStheir results open new perspectives for treating disorders associated with the disruption of these biological rhythms.

CK1δ protein and regulation of our biological clock

These researchers from Duke-NUS Medical School, in Singapore, and the University of California, in the United States, have demonstrated that the essential part of this regulation is located at the end of the CK1δ protein. The latter modulates our circadian rhythms by modifying other proteins involved in managing the internal clock. In addition to this, CK1δ itself can be modified, notably by the addition of phosphate groups, a process which alters its ability to regulate these other proteins. But until now, the precise mechanism of this regulation remained unclear.

Scientists have discovered that CK1δ exists in two slightly different forms, called isoforms δ1 and δ2, which differ by only 16 amino acids at their end, known as the C-terminal tail. Although these two versions vary little, their functions are very distinct. Using advanced spectroscopy techniques, scientists were able to take a closer look at these sequences and understand how they influence CK1δ activity.

“Our analysis allowed us to identify three specific sites on the tail of CK1δ where phosphate groups can attach, explain the researchers in a press release. When these sites are altered, CK1δ becomes less active, reducing its influence on circadian rhythms.” They specify that the δ1 form is more subject to internal regulation than the δ2: the tail of the δ1 version interacts more with the main part of the protein, which slows down its activity, while δ2 is less affected by this mechanism. When these sites are inhibited or suppressed, δ1 becomes more active, thereby altering circadian rhythms.

Better treatment of circadian rhythm disorders

“This finding shows how a small region of CK1δ can have a major influence on the overall activity of the protein. This self-regulation of CK1δ is therefore vital for maintaining its balanced activity, which in turn helps regulate our circadian rhythms .”

Note that the implications of the study go beyond sleep management. Indeed, CK1δ is also involved in other processes, such as cell division and the development of certain cancers. A better understanding of the regulation of CK1δ could therefore not only help to better treat circadian rhythm disorders (jet lag, insomnia, etc.), but also advance the fight against this type of disease.

“It’s about improving the quality of sleep, metabolism and, more broadly, our health and our daily life”according to the researchers, who now plan to study how external factors, such as diet or environmental changes, influence the sites of CK1δ modification. “This could offer practical solutions to better manage disruptions to circadian rhythms in everyday life.”