The reproductive hormones that trigger oocyte meiotic maturation and release from the ovary vary greatly between animal species. Identification of receptors for these maturation-inducing hormones (MIHs) and understanding how they initiate the largely conserved maturation process remain important challenges. In hydrozoan cnidarians including the jellyfish Clytia hemisphaerica, MIH comprises neuropeptides released from somatic cells of the gonad. We identified the receptor (MIHR) for these MIH neuropeptides in Clytia using cell culture-based "deorphanization" of candidate oocyte-expressed G protein-coupled receptors (GPCRs). MIHR mutant jellyfish generated using CRISPR-Cas9 editing had severe defects in gamete development or in spawning both in males and females. Female gonads, or oocytes isolated from MIHR mutants, failed to respond to synthetic MIH. Treatment with the cAMP analogue Br-cAMP to mimic cAMP rise at maturation onset rescued meiotic maturation and spawning. Injection of inhibitory antibodies to the alpha subunit of the Gs heterodimeric protein (GαS) into wild-type oocytes phenocopied the MIHR mutants. These results provide the molecular links between MIH stimulation and meiotic maturation initiation in hydrozoan oocytes. Molecular phylogeny grouped Clytia MIHR with a subset of bilaterian neuropeptide receptors, including neuropeptide Y, gonadotropin inhibitory hormone (GnIH), pyroglutamylated RFamide, and luqin, all upstream regulators of sexual reproduction. This identification and functional characterization of a cnidarian peptide GPCR advances our understanding of oocyte maturation initiation and sheds light on the evolution of neuropeptide-hormone systems.

中文翻译：

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AG蛋白偶联受体介导了水母Clytia中神经肽诱导的卵母细胞成熟。

触发卵母细胞减数分裂成熟并从卵巢释放的生殖激素在不同动物之间差异很大。鉴定这些成熟诱导激素（MIH）的受体并了解它们如何引发高度保守的成熟过程仍然是重要的挑战。在包括水母Clytia hemisphaerica在内的水生动物刺胞动物中，MIH包含从性腺体细胞释放的神经肽。我们使用候选卵母细胞表达的G蛋白偶联受体（GPCR）的基于细胞培养的“脱色化”，鉴定了Clytia中这些MIH神经肽的受体（MIHR）。使用CRISPR-Cas9编辑生成的MIHR突变水母在配子发育或雄性和雌性产卵中均存在严重缺陷。从MIHR突变体中分离出的雌性腺或卵母细胞，未能对合成MIH做出反应。用cAMP类似物Br-cAMP进行处理以模拟成熟时的cAMP升高，可以挽救减数分裂的成熟和产卵。将Gs异二聚体蛋白（GαS）的alpha亚基的抑制性抗体注射到表型MIHR突变体的野生型卵母细胞中。这些结果提供了MIH刺激和水生卵母细胞减数分裂成熟开始之间的分子联系。分子系统发育将Clytia MIHR与一个双侧神经肽受体子集分组，包括神经肽Y，促性腺激素抑制激素（GnIH），焦谷氨酰化RFamide和卢琴，这是性繁殖的所有上游调节剂。