Department of Medicine, Unit of Biochemistry, University of Fribourg, 1700 Fribourg, Switzerland.
Chronobiol Int. 2010 Jan;27(1):68-82. doi: 10.3109/07420521003648554.
A strong stimulus adjusting the circadian clock to the prevailing light-dark cycle is light. However, the circadian clock is reset by light only at specific times of the day. The mechanisms mediating such gating of light input to the CNS are not well understood. There is evidence that Ca(2+) ions play an important role in intracellular signaling mechanisms, including signaling cascades stimulated by light. Therefore, Ca(2+) is hypothesized to play a role in the light-mediated resetting of the circadian clock. Calbindin-D28k (CB; gene symbol: Calb1) is a Ca(2+) binding protein implicated in Ca(2+) homeostasis and sensing. The absence of this protein influences Ca(2+) buffering capacity of a cell, alters spatio-temporal aspects of intracellular Ca(2+) signaling, and hence might alter transmission of light information to the circadian clock in neurons of the suprachiasmatic nuclei (SCN). We tested mice lacking a functional Calb1 gene (Calb1(-/-)) and found an increased phase-delay response to light applied at circadian time (CT) 14 in these animals. This is accompanied by elevated induction of Per2 gene expression in the SCN. Period length and circadian rhythmicity were comparable between Calb1(-/-) and wild-type animals. Our findings indicate an involvement of CB in the signaling pathway that modulates the behavioral and molecular response to light.
强烈的刺激可以使生物钟与明暗周期同步，这种刺激就是光。然而，只有在一天中的特定时间，光才能重置生物钟。介导这种对中枢神经系统的光输入进行门控的机制还不太清楚。有证据表明，钙离子在细胞内信号转导机制中发挥着重要作用，包括光刺激引发的信号级联反应。因此，钙离子被假设在光介导的生物钟重置中发挥作用。钙结合蛋白 28k（CB；基因符号：Calb1）是一种与钙离子稳态和感知有关的钙离子结合蛋白。这种蛋白质的缺失会影响细胞的钙离子缓冲能力，改变细胞内钙离子信号的时空特征，从而可能改变光信息向视交叉上核（SCN）神经元中生物钟的传递。我们测试了缺乏功能性 Calb1 基因（Calb1(-/-)）的小鼠，发现这些动物在生物钟时间 14 时对光的相位延迟反应增加。这伴随着 SCN 中 Per2 基因表达的升高。Calb1(-/-)和野生型动物的周期长度和昼夜节律性相当。我们的发现表明 CB 参与了调节对光的行为和分子反应的信号通路。
