Corazonin signaling integrates energy homeostasis and lunar phase to regulate aspects of growth and sexual maturation in Platynereis

作者：Gabriele Andreatta, Caroline Broyart, Charline Borghgraef, Karim Vadiwala, Vitaly V. Kozin, Alessandra Polo, Andrea Bileck, Isabel Beets, Liliane Schoofs, Christopher Gerner, Florian Raible · 发表于：Proceedings of the National Academy of Sciences · 年份：2019 · DOI：10.1073/pnas.1910262116 · 被引用次数：64 · 研究领域：Neurobiology and Insect Physiology Research、Marine Biology and Environmental Chemistry、Physiological and biochemical adaptations

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 4 gnrh-like ( gnrhl ) preprohormone genes are expressed in specific and distinct neuronal clusters in the Platynereis brain. Moreover, ligand–receptor interaction analyses reveal a single Platynereis corazonin 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/gnrhl1 exhibits a particularly strong up-regulation in sexually mature animals, after feeding, and in specific lunar phases. Homozygous crz1/gnrhl1 knockout 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/Gn...