Intracellular Ca2+ regulates free-running circadian clock oscillation in vivo
Intracellular Ca2+ regulates free-running circadian clock oscillation in vivo
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DOI：
10.1523/jneurosci.3680-07.2007
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发表时间：
2007-11-14
影响因子：
5.3
通讯作者：
Nitabach, Michael N.
中科院分区：
文献类型：
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作者：
Harrisingh, Marie C.;Wu, Ying;Nitabach, Michael N.
虽然在植物和动物细胞中都观察到了细胞内钙信号动力学的昼夜振荡，但目前还不清楚钙信号是否在体内对细胞振荡本身起作用。为了解决这个问题，我们通过在转基因黑腹果蝇中靶向表达不同剂量的钙缓冲蛋白来改变体内昼夜节律起搏神经元细胞内钙信号的动态。起搏神经元的细胞内钙缓冲导致自由奔跑行为节律的剂量依赖性减慢，在最高剂量下，平均周期比对照组延长3小时。一种已知对细胞昼夜节律振荡至关重要的转录因子的有节奏的核积累也减慢了。我们还确定，钙缓冲与干扰钙调蛋白或钙调蛋白依赖的蛋白激酶II功能的基因操作具有协同作用。这些结果表明，细胞内钙信号在调节体内固有的细胞振荡中起着作用。
Although circadian oscillation in dynamics of intracellular Ca2+ signals has been observed in both plant and animal cells, it has remained unknown whether Ca2+ signals play an in vivo role in cellular oscillation itself. To address this question, we modified the dynamics of intracellular Ca2+ signals in circadian pacemaker neurons in vivo by targeted expression of varying doses of a Ca2+ buffer protein in transgenic Drosophila melanogaster. Intracellular Ca2+ buffering in pacemaker neurons results in dose-dependent slowing of free-running behavioral rhythms, with average period >3 h longer than control at the highest dose. The rhythmic nuclear accumulation of a transcription factor known to be essential for cellular circadian oscillation is also slowed. We also determined that Ca2+ buffering interacts synergistically with genetic manipulations that interfere with either calmodulin or calmodulin-dependent protein kinase II function. These results suggest a role for intracellular Ca2+ signaling in regulating intrinsic cellular oscillation in vivo.