Summary: Recent research from the University of Tokyo has identified key enzymes involved in the molecular regulation of sleep and wakefulness. Protein kinase A (PKA) was found to promote wakefulness, while dephosphorylation enzymes, including protein phosphatase 1 (PP1) and calcineurin, promote sleep. Using comprehensive gene knockout mice and viral vector experiments, researchers demonstrated that the balance between these enzymes at post-synapses plays a critical role in regulating daily sleep duration and sleep needs. These findings shed light on the molecular mechanisms underlying sleep-wake dynamics, offering potential targets for controlling sleep duration and sleepiness.
Key Takeaways:
- Key Enzymes Regulate Sleep and Wakefulness: Protein kinase A (PKA) decreases sleep duration and sleep needs, while PP1 and calcineurin promote sleep by increasing sleep duration and delta power, a measure of sleep needs.
- Competitive Role of Enzymes:PKA and the dephosphorylation enzymes PP1 and calcineurin act competitively at post-synapses to regulate daily sleep-wake cycles.
- Molecular Understanding of Sleep: This study advances the understanding of how sleep and wakefulness are controlled at the molecular level, paving the way for potential applications in managing sleep disorders or enhancing sleep regulation.
Recent research has observed that chemical modifications called phosphorylation of various proteins in brain neurons dynamically regulate in controlling sleep and wakefulness. On the other hand, it has not been fully elucidated the protein kinases that suppress sleep and the dephosphorylation enzymes that control sleep and wakefulness.
Animals, including humans, require a certain amount of sleep daily. When this sleep requirement is not met, humans experience sleep deprivation. However, the molecular mechanisms involved in sleep regulation remain unclear.
Discovering Key Enzymes in Sleep and Wakefulness
A research group at the Graduate School of Medicine of the University of Tokyo has discovered that protein kinase A (PKA) promotes wakefulness, while protein phosphatase 1 (PP1) and calcineurin, dephosphorylation enzymes, promote sleep in mammals.
Focusing on PKA and dephosphorylation enzymes, the research group created comprehensive gene knockout mice and conducted further experiments inducing the expression of functionally modified enzymes using viral vectors. Consequently, they found that PKA activation decreased sleep duration and delta power, and indicator of sleep needs.
Competitive Enzyme Actions Shape Sleep Duration
On the other hand, PP1 and calcineurin activation conversely increased sleep duration and delta power. In these sleep-wake promoting activities, it is essential that PKA, PP1, and calcineurin act at post-synapses responsible for information transmission between neurons. In addition, they demonstrated that PKA and PP1/calcineurin may work competitively to regulate the daily sleep duration.
This study, published in Nature, has revealed that the balance between sleep and wakefulness is regulated by the action of multiple enzymes, which is an important finding when considering how to control sleep duration and sleepiness on the molecular level.
This result was achieved in the Ueda Biological Timing Project, a research area of the Exploratory Research for Advanced Technology by the Japan Science and Technology Agency. Under this project, the Japan Science and Technology Agency is developing “systems biology for understanding humans” using sleep-wake rhythms as a model system in this project, aiming to understand “biological time” information that runs from molecules to individual humans living in society.
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