C. elegans Stress-Induced Sleep Emerges from the Collective Action of Multiple Neuropeptides.
C. elegans Stress-Induced Sleep Emerges from the Collective Action of Multiple Neuropeptides.
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DOI：
10.1016/j.cub.2016.07.048
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发表时间：
2016-09-26
期刊：
影响因子：
--
通讯作者：
Sternberg PW
中科院分区：
文献类型：
--
作者：
Nath RD;Chow ES;Wang H;Schwarz EM;Sternberg PW
睡眠调节的遗传基础仍然知之甚少。In C.在线虫中，细胞应激通过ALA神经元中表皮生长因子（EGF）依赖性激活EGF受体来诱导睡眠。这种神经元促进睡眠的下游机制尚不清楚。ALA的单细胞RNA-seq揭示了最高表达的富含ALA的基因编码神经肽。在这里，我们系统地研究了四种高度富集的神经肽：flp-7，nlp-8，flp-24和flp-13。当通过无效突变单独去除时，这些肽对压力诱导的睡眠几乎没有影响。然而，在nlp-8; flp-24; flp-13三重突变体动物中，应激诱导的睡眠被消除，表明这些神经肽共同控制应激诱导的睡眠。我们测试了这些神经肽基因的过度表达对睡眠期间调节的五种行为的影响-咽泵，排便，运动，头部运动和对厌恶刺激的回避反应-发现如果单独过度表达，三种神经肽（nlp-8，flp-24或flp-13）中的每一种都会诱导不同的睡眠相关行为。这些过度表达的结果提高了睡眠的各个组成部分可能由单个或组合的神经肽指定的可能性。睡眠是一种复杂的行为状态，需要多种行为的协调调节。Nath等研究了神经分泌细胞协同促进C.优雅他们发现，睡眠是由三种神经肽编码基因的集体作用产生的。
The genetic basis of sleep regulation remains poorly understood. In C. elegans, cellular stress induces sleep through Epidermal Growth Factor (EGF)-dependent activation of the EGF receptor in the ALA neuron. The downstream mechanism by which this neuron promotes sleep is unknown. Single-cell RNA-seq of ALA reveals that the most highly expressed, ALA-enriched genes encode neuropeptides. Here we have systematically investigated the four most highly enriched neuropeptides: flp-7, nlp-8, flp-24, and flp-13. When individually removed by null mutation, these peptides had little or no effect on stress-induced sleep. However, stress-induced sleep was abolished in the nlp-8; flp-24; flp-13 triple mutant animals, indicating that these neuropeptides work collectively in controlling stress-induced sleep. We tested the effect of overexpression of these neuropeptide genes on five behaviors modulated during sleep –pharyngeal pumping, defecation, locomotion, head movement, and avoidance response to an aversive stimulus – and found that if individually overexpressed, each of three neuropeptides (nlp-8, flp-24, or flp-13) induced a different suite of sleep-associated behaviors. These overexpression results raise the possibility that individual components of sleep might be specified by individual or combinations of neuropeptides. Sleep is a complex behavioral state that requires the coordinated regulation of multiple behaviors. Nath et al. investigate the downstream mechanism by which a neurosecretory cell coordinately promotes sleep in C. elegans. They discovered that sleep emerges from the collective action of three neuropeptide-encoding genes.
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DOI：
10.1895/wormbook.1.161.1
发表时间：
2013-08-13
期刊：
WormBook : the online review of C. elegans biology
影响因子：
--
作者：
Hobert, Oliver
通讯作者：
Hobert, Oliver
影响因子：
64.8
作者：
Raizen, David M.;Zimmerman, John E.;Pack, Allan I.
通讯作者：
Pack, Allan I.
影响因子：
16.2
作者：
LIU, KS;STERNBERG, PW
通讯作者：
STERNBERG, PW
影响因子：
25
作者：
Foltenyi, Krisztina;Greenspan, Ralph J.;Newport, John W.
通讯作者：
Newport, John W.
影响因子：
9.2
作者：
Allada, Ravi;Siegel, Jerome M.
通讯作者：
Siegel, Jerome M.