Afonso Dinis J S, Machado Daniel R, Koh Kyunghee
a Department of Neuroscience ; the Farber Institute for Neurosciences; and Kimmel Cancer Center; Thomas Jefferson University ; Philadelphia , PA USA.
b Life and Health Sciences Research Institute (ICVS); School of Health Sciences; University of Minho ; 4710-057 Braga , Portugal.
Fly (Austin). 2015;9(4):165-72. doi: 10.1080/19336934.2016.1153776.
Sleep is essential for health and cognition, but the molecular and neural mechanisms of sleep regulation are not well understood. We recently reported the identification of TARANIS (TARA) as a sleep-promoting factor that acts in a previously unknown arousal center in Drosophila. tara mutants exhibit a dose-dependent reduction in sleep amount of up to ∼60%. TARA and its mammalian homologs, the Trip-Br (Transcriptional Regulators Interacting with PHD zinc fingers and/or Bromodomains) family of proteins, are primarily known as transcriptional coregulators involved in cell cycle progression, and contain a conserved Cyclin-A (CycA) binding homology domain. We found that tara and CycA synergistically promote sleep, and CycA levels are reduced in tara mutants. Additional data demonstrated that Cyclin-dependent kinase 1 (Cdk1) antagonizes tara and CycA to promote wakefulness. Moreover, we identified a subset of CycA expressing neurons in the pars lateralis, a brain region proposed to be analogous to the mammalian hypothalamus, as an arousal center. In this Extra View article, we report further characterization of tara mutants and provide an extended discussion of our findings and future directions within the framework of a working model, in which a network of cell cycle genes, tara, CycA, and Cdk1, interact in an arousal center to regulate sleep.
睡眠对健康和认知至关重要，但睡眠调节的分子和神经机制尚未完全明确。我们最近报告称，已鉴定出塔兰尼斯（TARANIS，简称TARA）是一种促进睡眠的因子，它在果蝇一个此前未知的觉醒中枢发挥作用。tara突变体的睡眠量呈现剂量依赖性减少，最多可达约60%。TARA及其哺乳动物同源物，即与PHD锌指和/或溴结构域相互作用的转录调节因子（Trip-Br）家族蛋白质，主要作为参与细胞周期进程的转录共调节因子为人所知，并且含有一个保守的细胞周期蛋白A（CycA）结合同源结构域。我们发现tara和CycA协同促进睡眠，且tara突变体中CycA水平降低。更多数据表明，细胞周期蛋白依赖性激酶1（Cdk1）拮抗tara和CycA以促进觉醒。此外，我们在外侧部鉴定出一组表达CycA的神经元，该脑区被认为类似于哺乳动物的下丘脑，是一个觉醒中枢。在这篇补充观点文章中，我们报告了tara突变体的进一步特征，并在一个工作模型的框架内对我们的发现及未来方向进行了扩展讨论，在该模型中，细胞周期基因网络，即tara、CycA和Cdk1，在一个觉醒中枢相互作用以调节睡眠。
