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

Autor: Tone D; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka, Japan.; Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Ode KL; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka, Japan.; Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Zhang Q; Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Fujishima H; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka, Japan., Yamada RG; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka, Japan., Nagashima Y; Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.; Thermo Fisher Scientific K.K., Yokohama, Kanagawa, Japan., Matsumoto K; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka, Japan., Wen Z; Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Yoshida SY; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka, Japan.; Graduate school of Medicine, Osaka University, Suita, Osaka, Japan., Mitani TT; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka, Japan.; Graduate school of Medicine, Osaka University, Suita, Osaka, Japan., Arisato Y; Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.; Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Ohno RI; Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Ukai-Tadenuma M; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka, Japan., Yoshida Garçon J; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka, Japan., Kaneko M; Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Chuo-ku, Kobe, Hyogo, Japan., Shi S; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka, Japan.; Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Ukai H; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka, Japan., Miyamichi K; Laboratory for Comparative Connections, RIKEN Center for Biosystems Dynamics Research, Chuo-ku, Kobe, Hyogo, Japan., Okada T; Division of Molecular and Medical Genetics, Center for Gene and Cell Therapy, The Institute of Medical Science, the University of Tokyo, Minato-city, Tokyo, Japan., Sumiyama K; Laboratory for Mouse Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka, Japan., Kiyonari H; Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Chuo-ku, Kobe, Hyogo, Japan., Ueda HR; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka, Japan.; Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Jazyk: angličtina
Zdroj: PLoS biology [PLoS Biol] 2022 Oct 04; Vol. 20 (10), pp. e3001813. Date of Electronic Publication: 2022 Oct 04 (Print Publication: 2022).
DOI: 10.1371/journal.pbio.3001813
Abstrakt: The reduced sleep duration previously observed in Camk2b knockout mice revealed a role for Ca2+/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.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: H.R.U conducted a collaborative research project with Thermo Fisher Scientific Inc. Y.N. is an employee of Thermo Fisher Scientific, Inc. The company provided support in the form of salary for Y.N., and technical advice on the setup of mass spectrometers. However, the company did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Databáze: MEDLINE
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