Schibler Ueli
Department of Molecular Biology, University of Geneva, Geneva, Switzerland.
J Biol Rhythms. 2009 Feb;24(1):3-15. doi: 10.1177/0748730408329383.
The mammalian timing system is composed of a bodywide web of cell-autonomous and self-sustained oscillators. A master clock in the SCN synchronizes peripheral clocks through yet poorly understood molecular signaling pathways. In this lecture I shall present some of the experimental approaches we are employing to elucidate signaling routes through which the SCN may phase entrain peripheral clocks. These attempts unveiled several candidate pathways worth pursuing in future studies, including signaling through nuclear receptors, cytoskeleton components, Ca(2+), fibroblast growth factors, ubiquitin ligases, Sirtuin 1 (a redox-sensing histone deacetylase), RNA binding proteins, and body temperature.
哺乳动物的计时系统由遍布全身的细胞自主且自我维持的振荡器网络组成。视交叉上核(SCN)中的主时钟通过尚未完全了解的分子信号通路同步外周时钟。在本次讲座中,我将介绍我们正在采用的一些实验方法,以阐明SCN可能使外周时钟相位同步的信号传导途径。这些尝试揭示了几条值得在未来研究中深入探索的候选途径,包括通过核受体、细胞骨架成分、钙离子(Ca²⁺)、成纤维细胞生长因子、泛素连接酶、沉默调节蛋白1(一种氧化还原感应组蛋白脱乙酰酶)、RNA结合蛋白以及体温进行的信号传导。