Corazonin signaling integrates energy homeostasis and lunar phase to regulate aspects of growth and sexual maturation in Platynereis
Corazonin signaling integrates energy homeostasis and lunar phase to regulate aspects of growth and sexual maturation in Platynereis
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DOI：
10.1073/pnas.1910262116
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发表时间：
2020-01-14
影响因子：
11.1
通讯作者：
Raible，Florian
中科院分区：
文献类型：
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作者：
Andreatta，Gabriele;Broyart，Caroline;Raible，Florian
动物整合外部刺激与内部能量平衡来调节主要发育和生殖事件的分子机制仍然是个谜。我们调查了这方面的海洋鬃虫，Platynereis dumerilii，一个物种的性成熟受到代谢状态和月亮周期的严格调控。我们的具体重点是促性腺激素释放激素（GnRH）超家族的配体和受体。这个超家族的成员是触发脊椎动物性成熟的关键，但也调节无脊椎动物的生殖过程和能量稳态。在这里，我们表明，3的4 gnrh-like（gnrhl）preprohormone基因表达在特定的和不同的神经元簇在thePlatynereis脑。此外，配体-受体相互作用分析揭示了CRZ 1/GnRHL 1、CRZ 2/GnRHL 2和GnRHL 3可激活单一Platynereiscorazonin受体（CrzR）（以前被分类为AKH 1），而2种AKH型激素受体（GnRHR 1/AKHR 1和GnRHR 2/AKHR 2）仅对单一配体产生应答（GnRH 2/GnRHL 4）. Crz 1/gnrhl 1在性成熟动物、进食后和特定月相中表现出特别强烈的上调。homozygouz 1/gnrhl 1基因敲除动物表现出明显的成熟延迟，生长减少，再生减弱。通过结合蛋白质组学和基因表达分析，我们确定参与碳水化合物代谢的酶作为CRZ 1/GnRHL 1信号传导的转录靶点。我们的数据表明，PlatynereisCRZ 1/GnRHL 1协调糖蛋白周转和能量平衡与生长和性成熟，整合代谢和发育需求与蠕虫的每月周期。
The molecular mechanisms by which animals integrate external stimuli with internal energy balance to regulate major developmental and reproductive events still remain enigmatic. We investigated this aspect in the marine bristleworm,Platynereis dumerilii, a species where sexual maturation is tightly regulated by both metabolic state and lunar cycle. Our specific focus was on ligands and receptors of the gonadotropin-releasing hormone (GnRH) superfamily. Members of this superfamily are key in triggering sexual maturation in vertebrates but also regulate reproductive processes and energy homeostasis in invertebrates. Here we show that 3 of the 4gnrh-like(gnrhl) preprohormone genes are expressed in specific and distinct neuronal clusters in thePlatynereisbrain. Moreover, ligand–receptor interaction analyses reveal a singlePlatynereiscorazonin receptor (CrzR) to be activated by CRZ1/GnRHL1, CRZ2/GnRHL2, and GnRHL3 (previously classified as AKH1), whereas 2 AKH-type hormone receptors (GnRHR1/AKHR1 and GnRHR2/AKHR2) respond only to a single ligand (GnRH2/GnRHL4).Crz1/gnrhl1exhibits a particularly strong up-regulation in sexually mature animals, after feeding, and in specific lunar phases. Homozygouscrz1/gnrhl1knockout animals exhibit a significant delay in maturation, reduced growth, and attenuated regeneration. Through a combination of proteomics and gene expression analysis, we identify enzymes involved in carbohydrate metabolism as transcriptional targets of CRZ1/GnRHL1 signaling. Our data suggest thatPlatynereisCRZ1/GnRHL1 coordinates glycoprotein turnover and energy homeostasis with growth and sexual maturation, integrating both metabolic and developmental demands with the worm’s monthly cycle.