The RFamide receptor DMSR-1 regulates stress-induced sleep in C. elegans
The RFamide receptor DMSR-1 regulates stress-induced sleep in C. elegans
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DOI：
10.7554/elife.19837
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发表时间：
2017-01-17
期刊：
影响因子：
7.7
通讯作者：
Raizen, David M.
中科院分区：
文献类型：
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作者：
Iannacone, Michael J.;Beets, Isabel;Raizen, David M.
为了应对导致细胞应激的环境，动物会进行睡眠行为，以促进从应激中恢复。在秀丽隐杆线虫中，应激诱导的睡眠（SIS）由ALA神经元的细胞因子激活调节，ALA神经元释放以酰胺化的精氨酸-苯丙氨酸（RFamide）C-末端基序为特征的FLP-13神经肽。通过对损害FLP-13神经肽的致眠作用的突变体进行无偏遗传筛选，我们鉴定了基因dmsr-1，其编码类似于昆虫RFamide受体的G蛋白偶联受体。DMSR-1在细胞培养物中被FLP-13肽激活，是体内SIS所需的，在几种促进唤醒的神经元中非突触地表达，并且可能偶联到Gi/o异源三聚体G蛋白。我们的数据扩展了我们对单个神经内分泌细胞如何协调整个生物体行为反应的理解，并表明类似的信号原理可能在其他生物体中起作用，以调节疾病期间的睡眠。
In response to environments that cause cellular stress, animals engage in sleep behavior that facilitates recovery from the stress. In Caenorhabditis elegans, 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 dmsr-1, 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 in vivo, 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.