RPamide neuropeptides NLP-22 and NLP-2 act through GnRH-like receptors to promote sleep and wakefulness in C. elegans
RPamide neuropeptides NLP-22 and NLP-2 act through GnRH-like receptors to promote sleep and wakefulness in C. elegans
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DOI：
10.1038/s41598-020-66536-2
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发表时间：
2020-06
影响因子：
4.6
通讯作者：
Petrus Van der Auwera;L. Frooninckx;Kristen Buscemi;Ryan T Vance;Jan Watteyne;Olivier Mirabeau;L. Temmerman;Wouter De Haes;Luca Fancsalszky;A. Gottschalk;D. Raizen;M. Nelson;L. Schoofs;Isabel Beets
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作者：
Petrus Van der Auwera;L. Frooninckx;Kristen Buscemi;Ryan T Vance;Jan Watteyne;Olivier Mirabeau;L. Temmerman;Wouter De Haes;Luca Fancsalszky;A. Gottschalk;D. Raizen;M. Nelson;L. Schoofs;Isabel Beets
睡眠和清醒是基本的行为状态，其潜在的分子原理正在慢慢阐明。这些状态之间的转换需要多个神经化学和调节系统的协调。秀丽隐杆线虫的睡眠发生在幼虫的过渡阶段，称为嗜睡期，并由致睡神经肽诱导。在这里，我们确定了两种相反的神经肽/受体信号通路：NLP-22促进行为静止，而NLP-2通过促性腺激素释放激素（GnRH）相关受体的信号传导促进昏睡时的运动。NLP-2和NLP-22都属于RPamide神经肽家族，与双侧GnRH、脂肪动力学激素（adipokinetic hormone， AKH）和corazonin家族的神经肽具有序列相似性。在细胞受体激活试验中，RPamide神经肽剂量依赖性地激活GnRH/ akh样受体GNRR-3和GNRR-6。此外，nlp-22诱导的运动静止需要受体nrr-6。相比之下，nlp-2过表达引起的清醒可以通过删除gnrr-3or nrp -6来减少。nlp-2在一对嗅觉AWA神经元中表达，并以幼虫周期为周期，如nlp-22所报道，nlp-22在RIA中表达。我们的数据表明，促睡眠NLP-22神经肽通过GNRR-6发出信号，而NLP-2神经肽的促醒作用需要GNRR-3和GNRR-6。
Sleep and wakefulness are fundamental behavioral states of which the underlying molecular principles are becoming slowly elucidated. Transitions between these states require the coordination of multiple neurochemical and modulatory systems. InCaenorhabditis eleganssleep occurs during a larval transition stage called lethargus and is induced by somnogenic neuropeptides. Here, we identify two opposing neuropeptide/receptor signaling pathways: NLP-22 promotes behavioral quiescence, whereas NLP-2 promotes movement during lethargus, by signaling through gonadotropin-releasing hormone (GnRH) related receptors. Both NLP-2 and NLP-22 belong to the RPamide neuropeptide family and share sequence similarities with neuropeptides of the bilaterian GnRH, adipokinetic hormone (AKH) and corazonin family. RPamide neuropeptides dose-dependently activate the GnRH/AKH-like receptors GNRR-3 and GNRR-6 in a cellular receptor activation assay. In addition,nlp-22-induced locomotion quiescence requires the receptorgnrr-6. By contrast, wakefulness induced bynlp-2overexpression is diminished by deletion of eithergnrr-3orgnrr-6.nlp-2is expressed in a pair of olfactory AWA neurons and cycles with larval periodicity, as reported fornlp-22, which is expressed in RIA. Our data suggest that the somnogenic NLP-22 neuropeptide signals through GNRR-6, and that both GNRR-3 and GNRR-6 are required for the wake-promoting action of NLP-2 neuropeptides.