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Tango10, Sleep disorders are caused by mutations in the gene for diligence.

2022-02-05 16:41

- Discovery of 쁔ango10 gene mutation in 쁞usy-run fruit flies
- The ability to synchronize the biological clock is broken
- Relevance to sleep disorders remains a research subject

Is Sleep Disorder Caused by Mutations in the 'Diligent' Gene?
The circadian rhythm regulation model by Tango10 The biological clock genes that operate the molecular clock through the regulation of 24-hour cycle gene expression control the expression of 'Tango10-Cullin 3', a ubiquitination enzyme protein complex at the axon terminal of the biological clock neuron. regulated. Tango10 controls the excitability of biological clock neurons through the same K+ ion channel as Shaker/Shal, and regulates the circadian secretion of PDF, a biological clock neuromodulatory peptide. Tango10 regulates 24-hour cycle animal behavior by linking molecular clocks and circadian neuroplasticity through protein ubiquitination.

A broken component has been discovered in a new biological clock that regulates the circadian rhythm of sleep.

On November 22, 2021, a team led by Professor Jong-bin Lee and Jeong-hoon Lim of the Department of Life Sciences at UNIST in Korea discovered the 'Tango10' gene mutation in the 'Diligent Drosophila', which sleeps abnormally, and identified the neurobiological principle after 10 years of research. work said

When the Tango10 gene breaks down, the pacemaker neurons remain excited, disrupting the sleep cycle. A pacemaker neuron is a nerve cell that transmits 24-hour cycle information to other nerve cells in the brain so that all nerve cells have the same cycle.
According to the research team, living things have a circadian clock that responds to environmental changes during the day and night. It is thanks to the biological clock that morning glory blooms during the day and fades at night. Important physiological functions such as human sleep, brain function, and metabolism are also regulated by the biological clock. Scientists who discovered biological clock-actuating genes and proteins in fruit fly experiments have even been awarded the Nobel Prize in Physiology.

The research team also discovered a 'busy-run' fruit fly with a mutation in the Tango10 gene while searching for a yellow fruit fly mutant 10 years ago. Due to the characteristic of sleeping very little, the mutant fruit fly was named after the Korean word for 쐂iligence.

As a result of the experiment, the pacemaker neurons of this mutant fruit fly had a dysfunctional ability to synchronize the biological clock. There was no change in the shape of nerve endings (neural plasticity) that should be seen in a 24-hour cycle, and the excitability of nerve cells was excessively increased.

The PDF (Pigment-Dispersing Factor) neuropeptide, a substance secreted from nerve endings to synchronize the biological clocks of other cells, was also not normal. PDF must be repeatedly accumulated and secreted in a 24-hour cycle, and the Tango10 mutant continued to accumulate PDF in nerve terminals.

The researchers found that the Tango10 gene is involved in the function of these pacemaker neurons and sleep regulation by mediating protein ubiquitination. Protein ubiquitination is a reaction that breaks down used proteins.

We also found the Tango10-Cullin3 protein complex, which is strong evidence to prove this. Cullin3 is an enzyme widely known for attaching ubiquitin to proteins. This protein complex was accumulated at the end of the pacemaker neurons in a 24-hour cycle.

The first author, Dr. Jongbin Lee (Research Professor, Department of Life Sciences, UNIST) said, 쏷he results of this experiment show that the Tango10-Cullin3 complex transmits time information that determines the sleep cycle by regulating protein ubiquitination at the synapse (the part that connects neurons). Evidence to be expected.

Through this, the research team also proposed a new circadian rhythm control model.

The Tango10 gene controls the excitability of pacemaker neurons, and through this excitability, regulates the secretion of PDF, a neuromodulatory peptide that transmits time information, thereby maintaining circadian rhythmic behaviors such as sleep.

The amount of potassium ions in neurons plays an important role in the regulation of neuronal excitability, and it is hypothesized that Tango10 controls this cell excitability through specific potassium ion channels. The research team also proved this hypothesis through electrophysiology experiments and computational biology modeling.

He explained, 쏷he gene that plays the role of the gear (gear) that turns the biological clock has already been revealed through Nobel Prize-winning research. did.

The research team continued, "If we find the target protein that is actually degraded by Tango10-Cullin3 and further investigate the relationship with human circadian sleep disorder, we will be able to find clues about the treatment of sleep disorders, etc."
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