Mutations in the “lark gene” have helped to understand how circadian rhythms work
Circadian, or diurnal, cycles regulate many processes in the human body, but how exactly - is not quite clear. In a new study, scientists have established the mechanisms of the gene associated with the hereditary “lark syndrome” - early awakening and falling asleep. It turns out that the regulation of the diurnal cycle is due to a special “phosphoswitch” - the transitions of protein Per from one state to another.
Daily rhythms are of great importance for human health. They allow to synchronize various physiological processes, provide alternation of sleep and wakefulness and rest necessary for the organism.
However, how exactly do rhythms are regulated and reorganized - for example, when moving to another time zone or changing the length of daylight hours? This question was answered by the authors of the article, who learned a lot about the work of the “biological clock” at the molecular level.
To understand the regulation of the diurnal cycle helped gene associated with a hereditary disease - it is the so-called lark syndrome, or Familial Advanced Sleep Phase Syndrome (Familial Advanced Sleep Phase Syndrome, FASP). Those who have the disease have mutations in the Per1 gene, specifically in the region of the gene, which is called the same name as their disease - FASP. Because of them, such people suffer from premature awakening and falling asleep - they are pronounced “larks”. Their daily cycles are noticeably shorter: they last not 24 but only about 20 hours.
People with FASP seem to live with a constant jetlag, i.e. with a “biological clock” that cannot be adjusted. Scientists have known about this “breakdown” of biorhythms for more than 20 years, but its details at the level of molecules have only now become known.
In the new work used cell cultures - both human and Drosophila. It turns out that in the cells of this popular among biologists insect has a very similar system of setting the “biological chronometer”.
Proteins called Period (also PER) play a key role in human circadian rhythms. Their state is changed due to the attachment of phosphoric acid residues by a special enzyme - casein kinase 1. This so-called phosphorylation of PER proteins can both make them stable and accelerate their destruction and thus reduce the duration of the diurnal cycle.
The scientists found that the Per protein actually has two regions to which phosphoric acid residues can attach. If they connect to the FASP region mutated in “hereditary larks,” the protein becomes more stable and the activity of the casein kinase enzyme decreases. If phosphorylation occurs on a different region, Per degrades more quickly.
It is the dynamic balance between the stability and decay of this protein that maintains the desired length of the diurnal cycle and allows you to change it if necessary.
Scientists are convinced that the new data on the work of the “molecular clock” will help in finding ways to treat various sleep disorders and biological rhythms.