부산대학교 도서관

The reduced sleep duration previously observed in Camk2b knockout mice revealed a role for Ca.sup.2+ /calmodulin-dependent protein kinase II (CaMKII)[beta] as a sleep-promoting kinase. However, the underlying mechanism by which CaMKII[beta] supports sleep regulation is largely unknown. Here, we demonstrate that activation or inhibition of CaMKII[beta] can increase or decrease sleep duration in mice by almost 2-fold, supporting the role of CaMKII[beta] as a core sleep regulator in mammals. Importantly, we show that this sleep regulation depends on the kinase activity of CaMKII[beta]. A CaMKII[beta] 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 CaMKII[beta] differently control sleep induction and maintenance processes, leading us to propose a "phosphorylation hypothesis of sleep" for the molecular control of sleep in mammals.
Author(s): Daisuke Tone 1,2, Koji L. Ode 1,2, Qianhui Zhang 2, Hiroshi Fujishima 1, Rikuhiro G. Yamada 1, Yoshiki Nagashima 2,3, Katsuhiko Matsumoto 1, Zhiqing Wen 2, Shota Y. Yoshida […]