Distinct phosphorylation states of mammalian CaMKIIβ control the induction and maintenance of sleep

The reduced sleep duration previously observed in Camk2b knockout mice revealed a role for Ca 2+ /calmodulin-dependent protein kinase II (CaMKII)β as a sleep-promoting kinase. However, the underlying mechanism by which CaMKIIβ supports sleep regulation is largely unknown. Here, we demonstrate that a...

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Published in:PLoS biology 2022-10, Vol.20 (10), p.e3001813-e3001813
Main Authors: Tone, Daisuke, Ode, Koji L., Zhang, Qianhui, Fujishima, Hiroshi, Yamada, Rikuhiro G., Nagashima, Yoshiki, Matsumoto, Katsuhiko, Wen, Zhiqing, Yoshida, Shota Y., Mitani, Tomoki T., Arisato, Yuki, Ohno, Rei-ichiro, Ukai-Tadenuma, Maki, Yoshida Garçon, Junko, Kaneko, Mari, Shi, Shoi, Ukai, Hideki, Miyamichi, Kazunari, Okada, Takashi, Sumiyama, Kenta, Kiyonari, Hiroshi, Ueda, Hiroki R.
Format: Article
Language:English
Subjects:
Biology and Life Sciences
Ca2+/calmodulin-dependent protein kinase II
Calcium ions
Calcium-binding protein
Calmodulin
Efficiency
Gene expression
Hypotheses
Kinases
Maintenance
Mammals
Medicine and Health Sciences
Mimicry
Mutants
Phosphorylation
Physiology
Proteins
Research and Analysis Methods
Sleep
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Summary:The reduced sleep duration previously observed in Camk2b knockout mice revealed a role for Ca 2+ /calmodulin-dependent protein kinase II (CaMKII)β as a sleep-promoting kinase. However, the underlying mechanism by which CaMKIIβ supports sleep regulation is largely unknown. Here, we demonstrate that activation or inhibition of CaMKIIβ can increase or decrease sleep duration in mice by almost 2-fold, supporting the role of CaMKIIβ as a core sleep regulator in mammals. Importantly, we show that this sleep regulation depends on the kinase activity of CaMKIIβ. A CaMKIIβ mutant mimicking the constitutive-active (auto)phosphorylation state promotes the transition from awake state to sleep state, while mutants mimicking subsequent multisite (auto)phosphorylation states suppress the transition from sleep state to awake state. These results suggest that the phosphorylation states of CaMKIIβ differently control sleep induction and maintenance processes, leading us to propose a “phosphorylation hypothesis of sleep” for the molecular control of sleep in mammals.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.3001813