Iannacone Michael J, Beets Isabel, Lopes Lindsey E, Churgin Matthew A, Fang-Yen Christopher, Nelson Matthew D, Schoofs Liliane, Raizen David M
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.
Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.
Elife. 2017 Jan 17;6:e19837. doi: 10.7554/eLife.19837.
In response to environments that cause cellular stress, animals engage in sleep behavior that facilitates recovery from the stress. In , stress-induced sleep(SIS) is regulated by cytokine activation of the ALA neuron, which releases FLP-13 neuropeptides characterized by an amidated arginine-phenylalanine (RFamide) C-terminus motif. By performing an unbiased genetic screen for mutants that impair the somnogenic effects of FLP-13 neuropeptides, we identified the gene , which encodes a G-protein coupled receptor similar to an insect RFamide receptor. DMSR-1 is activated by FLP-13 peptides in cell culture, is required for SIS , is expressed non-synaptically in several wake-promoting neurons, and likely couples to a Gi/o heterotrimeric G-protein. Our data expand our understanding of how a single neuroendocrine cell coordinates an organism-wide behavioral response, and suggest that similar signaling principles may function in other organisms to regulate sleep during sickness.
为应对导致细胞应激的环境，动物会进入睡眠行为以促进从应激中恢复。在[具体研究中]，应激诱导睡眠（SIS）由ALA神经元的细胞因子激活所调节，该神经元释放具有酰胺化精氨酸 - 苯丙氨酸（RFamide）C末端基序特征的FLP - 13神经肽。通过对损害FLP - 13神经肽促眠作用的突变体进行无偏向遗传筛选，我们鉴定出了[具体基因名称]基因，它编码一种类似于昆虫RFamide受体的G蛋白偶联受体。DMSR - 1在细胞培养中被FLP - 13肽激活，是SIS所必需的，在几个促进觉醒的神经元中非突触性表达，并且可能与Gi/o异源三聚体G蛋白偶联。我们的数据扩展了我们对单个神经内分泌细胞如何协调全生物体行为反应的理解，并表明类似的信号传导原理可能在其他生物体中起作用，以在患病期间调节睡眠。
