PDF(Pubmed)
Abstract：
Circadian rhythms are endogenous oscillations in nearly all organisms, from prokaryotes to humans, allowing them to adapt to cyclical environments for close to 24 h. Circadian rhythms are regulated by a central clock, based on a transcription-translation feedback loop. One important protein in the central loop in metazoan clocks is PERIOD, which is regulated in part by Casein kinase 1ε/δ (CK1ε/δ) phosphorylation. In the nematode Caenorhabditis elegans, period and casein kinase 1ε/δ are conserved as lin-42 and kin-20, respectively. Here, we studied the involvement of lin-42 and kin-20 in the circadian rhythms of the adult nematode using a bioluminescence-based circadian transcriptional reporter. We show that mutations of lin-42 and kin-20 generate a significantly longer endogenous period, suggesting a role for both genes in the nematode circadian clock, as in other organisms. These phenotypes can be partially rescued by overexpression of either gene under their native promoter. Both proteins are expressed in neurons and epidermal seam cells, as well as in other cells. Depletion of LIN-42 and KIN-20, specifically in neuronal cells after development, was sufficient to lengthen the period of oscillating sur-5 expression. Therefore, we conclude that LIN-42 and KIN-20 are critical regulators of the adult nematode circadian clock through neuronal cells.
摘要：
昼夜节律是几乎所有生物体的内源性振荡，从原核生物到人类,使它们能够适应接近24小时的周期性环境。昼夜节律由中央时钟调节，基于转录-翻译反馈循环。在后生动物钟的中心环中一个重要的蛋白质是PERIOD,其部分受酪蛋白激酶1ε/δ(CK1ε/δ)磷酸化调节。在线虫秀丽隐杆线虫中，周期和酪蛋白激酶1ε/δ分别保留为lin-42和kin-20。这里,我们使用基于生物发光的昼夜节律转录报告子研究了lin-42和kin-20在成年线虫昼夜节律中的参与。我们发现lin-42和kin-20的突变会产生明显更长的内源期，表明这两个基因在线虫生物钟中的作用，就像其他生物一样。这些表型可以通过在其天然启动子下过表达任一基因来部分挽救。这两种蛋白质都在神经元和表皮缝细胞中表达，以及其他细胞。LIN-42和KIN-20的耗竭，特别是在发育后的神经元细胞中，足以延长sur-5表达振荡的周期。因此,我们得出的结论是，LIN-42和KIN-20是通过神经元细胞的成年线虫昼夜节律的关键调节因子。
