Deep conservation of genes required for both Drosphila melanogaster and Caenorhabditis elegans sleep includes a role for dopaminergic signaling.
Deep conservation of genes required for both Drosphila melanogaster and Caenorhabditis elegans sleep includes a role for dopaminergic signaling.
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DOI：
10.5665/sleep.3990
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发表时间：
2014-09
期刊：
影响因子：
5.6
通讯作者：
Komudi Singh;Jennifer Y Ju;Melissa B. Walsh;Michael A. DiIorio;A. Hart
中科院分区：
文献类型：
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作者：
Komudi Singh;Jennifer Y Ju;Melissa B. Walsh;Michael A. DiIorio;A. Hart
目标 类睡眠行为的跨物种保守性预测睡眠背后保守分子机制的存在。然而，保护的实验证据有限。在这里，直接检验这个预测。测量和结果 在昏睡期间，秀丽隐杆线虫会自发地短暂睡眠，期间穿插着自发运动。我们鉴定了果蝇睡眠所需的 26 个基因。基于相似性选择了 20 个直系同源秀丽隐杆线虫基因。评估了它们对线虫最后一次幼虫昏睡期间睡眠和觉醒的影响。 20 个最相似的基因改变了睡眠时间和觉醒阈值。在 18 个案例中，变化方向与之前发表的果蝇研究一致。此外，我们描绘了多巴胺调节睡眠和觉醒的保守遗传途径。在秀丽隐杆线虫神经元中，G-α S、腺苷酸环化酶和蛋白激酶 A 在 D1 多巴胺受体下游发挥作用来调节这些行为。最后，本文检查的基因的定量分析表明，线虫的唤醒阈值与昏睡期间的睡眠量直接相关。然而，发作持续时间变化不大，并且与唤醒阈值不相关。结论 这里提出的综合分析表明，保守的基因和途径是无脊椎动物睡眠所必需的，很可能是整个动物界的睡眠所必需的。这项研究中描绘的遗传途径涉及 G-alpha S 和先前已知的睡眠中多巴胺信号下游的基因。对静止的各种成分的定量分析表明，相互依赖或相同的细胞和分子机制可能调节觉醒和睡眠进入。
OBJECTIVES Cross-species conservation of sleep-like behaviors predicts the presence of conserved molecular mechanisms underlying sleep. However, limited experimental evidence of conservation exists. Here, this prediction is tested directly. MEASUREMENTS AND RESULTS During lethargus, Caenorhabditis elegans spontaneously sleep in short bouts that are interspersed with bouts of spontaneous locomotion. We identified 26 genes required for Drosophila melanogaster sleep. Twenty orthologous C. elegans genes were selected based on similarity. Their effect on C. elegans sleep and arousal during the last larval lethargus was assessed. The 20 most similar genes altered both the quantity of sleep and arousal thresholds. In 18 cases, the direction of change was concordant with Drosophila studies published previously. Additionally, we delineated a conserved genetic pathway by which dopamine regulates sleep and arousal. In C. elegans neurons, G-alpha S, adenylyl cyclase, and protein kinase A act downstream of D1 dopamine receptors to regulate these behaviors. Finally, a quantitative analysis of genes examined herein revealed that C. elegans arousal thresholds were directly correlated with amount of sleep during lethargus. However, bout duration varies little and was not correlated with arousal thresholds. CONCLUSIONS The comprehensive analysis presented here suggests that conserved genes and pathways are required for sleep in invertebrates and, likely, across the entire animal kingdom. The genetic pathway delineated in this study implicates G-alpha S and previously known genes downstream of dopamine signaling in sleep. Quantitative analysis of various components of quiescence suggests that interdependent or identical cellular and molecular mechanisms are likely to regulate both arousal and sleep entry.