CaMKII is essential for the cellular clock and coupling between morning and evening behavioral rhythms.
CaMKII is essential for the cellular clock and coupling between morning and evening behavioral rhythms.
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DOI：
10.1101/gad.237511.114
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发表时间：
2014-05-15
影响因子：
10.5
通讯作者：
Fukada Y
中科院分区：
文献类型：
--
作者：
Kon N;Yoshikawa T;Honma S;Yamagata Y;Yoshitane H;Shimizu K;Sugiyama Y;Hara C;Kameshita I;Honma K;Fukada Y
哺乳动物的日常行为节律由位于视交叉上核 (SCN) 的中央生物钟控制，钙被认为在 SCN 的振荡中发挥作用。康等人。现在发现 Ca2+/钙调蛋白依赖性蛋白激酶 II (CaMKII) 活性促进 CLOCK 和 BMAL1 的二聚化，并且对于 SCN 振荡器之间的细胞振荡和同步至关重要。激酶死亡的 CaMKIIα 削弱了行为节律，并引起早晨和晚上活动节律之间的脱钩。哺乳动物的日常行为节律由位于视交叉上核（SCN）的中央生物钟控制。即使在持续的黑暗中，行为节律也会持续存在，并且由于决定早晨和晚上活动的两个振荡器之间的耦合而具有稳定的活动时间。越来越多的证据支持 Ca2+ 在 SCN 剧烈振荡中的先决作用，但潜在的分子机制仍然难以捉摸。在这里，我们发现 Ca2+/钙调蛋白依赖性蛋白激酶 II (CaMKII) 活性不仅对于细胞振荡至关重要，而且对于 SCN 中振荡器之间的同步也至关重要。小鼠 CaMKIIα 的激酶死亡突变削弱了行为节律，并引起早晨和晚上活动节律之间的脱钩，有时导致心律失常。在突变的 SCN 中，左右核表现出非耦合振荡。细胞和生化分析表明，Ca2+-钙调蛋白-CaMKII 信号传导通过促进昼夜运动输出周期 kaput (CLOCK) 和脑和肌肉 Arnt 样蛋白 1 (BMAL1) 的二聚化，有助于激活 E-box 依赖性基因表达。这些结果证明了 CaMKII 作为细胞自主发条的组成部分和作为整合昼夜行为活动的同步器的双重作用。
Daily behavioral rhythms in mammals are governed by the central circadian clock located in the suprachiasmatic nucleus (SCN), and calcium is thought to play a role in the oscillation of the SCN. Kon et al. now find that Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity promotes dimerization of CLOCK and BMAL1 and is essential for the cellular oscillation and synchronization among oscillators in the SCN. Kinase-dead CaMKIIα weakened the behavioral rhythmicity and elicited decoupling between the morning and evening activity rhythms. Daily behavioral rhythms in mammals are governed by the central circadian clock, located in the suprachiasmatic nucleus (SCN). The behavioral rhythms persist even in constant darkness, with a stable activity time due to coupling between two oscillators that determine the morning and evening activities. Accumulating evidence supports a prerequisite role for Ca2+ in the robust oscillation of the SCN, yet the underlying molecular mechanism remains elusive. Here, we show that Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity is essential for not only the cellular oscillation but also synchronization among oscillators in the SCN. A kinase-dead mutation in mouse CaMKIIα weakened the behavioral rhythmicity and elicited decoupling between the morning and evening activity rhythms, sometimes causing arrhythmicity. In the mutant SCN, the right and left nuclei showed uncoupled oscillations. Cellular and biochemical analyses revealed that Ca2+–calmodulin–CaMKII signaling contributes to activation of E-box-dependent gene expression through promoting dimerization of circadian locomotor output cycles kaput (CLOCK) and brain and muscle Arnt-like protein 1 (BMAL1). These results demonstrate a dual role of CaMKII as a component of cell-autonomous clockwork and as a synchronizer integrating circadian behavioral activities.
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影响因子：
5.3
作者：
Harrisingh, Marie C.;Wu, Ying;Nitabach, Michael N.
通讯作者：
Nitabach, Michael N.
影响因子：
10.5
作者：
Kondratov, RV;Chernov, MV;Antoch, MP
通讯作者：
Antoch, MP
影响因子：
64.8
作者：
Grima, B;Chèlot, E;Rouyer, F
通讯作者：
Rouyer, F
DOI：
10.1006/bbrc.1996.0536
发表时间：
1996-04-05
影响因子：
3.1
作者：
Marley, PD;Thomson, KA
通讯作者：
Thomson, KA
影响因子：
3.4
作者：
Michel, Stephan;Marek, Roger;Meijer, Johanna H.
通讯作者：
Meijer, Johanna H.