A G protein–coupled receptor mediates neuropeptide-induced oocyte maturation in the jellyfish Clytia

Abstract

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 G s heterodimeric protein (Gα S ) 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. OPEN ACCESSCitation: Quiroga Artigas G, Lapébie P, Leclère L, Bauknecht P, Uveira J, Chevalier S, et al. (2020) A G protein-coupled receptor mediates neuropeptide-induced oocyte maturation in the jellyfish Clytia. PLoS Biol 18(3): e3000614. https:// ) to TM, as well as core funding kinase complex assures meiotic progression from prophase I arrest into M phase, while parallel Mos-MAP kinase activation steers polar body formation as well as cytostatic arrest once maturation is complete [2,3]. In contrast, the upstream physiological processes vary widely, as does the molecular nature of the maturation-inducing hormones (MIHs) that act on the oocyte to trigger maturation [1,4]. This reflects clade-specific acquisition of endocrine tissues such as ovarian follicles, the corpus cardiacum/corpus allatum in insects, or the pituitary in vertebrates [5,6]. These tissues act downstream of other neuroendocrine sites such as the vertebrate hypothalamus to integrate environmental, behavioral, and physiological information in order to achieve optimal conditions for gamete development and release [7]. The complex evolutionary history of hormonal reproductive regulation has made it challenging to unravel the crucial regulatory events operating within the oocyte at the onset of maturation.G protein-coupled receptors (GPCRs), the largest superfamily of integral ...

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“…Only one of these is shared with other eumetazoans, the extracellular signalling molecule Trunk (a paralog of prothoracicotropic hormones) [32]. At least six peptide families trace back to the cnidarian-bilaterian common ancestor (RFamide, VWamide, PRXamide, insulin-like peptides, eclosion hormone (EH), bursicon) [32][33][34][35]. These in general show a many-to-many relationship to bilaterian peptide and receptor families.…”

“…These in general show a many-to-many relationship to bilaterian peptide and receptor families. For example, a group of cnidarian receptors including the Clytia hemisphaerica maturation-inducing hormone receptor (MIHR) is sister to a bilaterian clade containing receptors for luqin, NPF, QRFP, tachykinin, FMRFa and NPY peptides [ 30 , 33 ]. Placozoans (millimetre-sized flat animals with no muscles or neurons) also contain several neuropeptides [ 26 , 32 , 36 , 37 ].…”

“…An increase in ambient light (at dawn in a natural setting) leads to the release of MIH, a process that is defective in opsin mutant jellyfish [ 79 ]. The peptide activates a GPCR receptor (the MIH receptor) expressed in the oocytes to trigger spawning [ 33 ].…”

“…The elongations are filled with neuropeptide-containing vesicles [ 79 ] ( figure 4 d ). The tiling of the tissue together with the projections likely ensure a uniform release of MIH following a dark–light transition to uniformly stimulate the target cells, the maturing oocytes expressing the MIH receptor [ 33 ].…”

Managing the Oocyte Meiotic Arrest—Lessons from Frogs and Jellyfish

“…Reflecting this molecular diversity of MIHs, their receptors on the oocyte surface appear to be of several distinct types, and to act via different second messenger systems. Nevertheless, as detailed below, it is striking that receptors of the G-protein coupled receptor (GPCR) class, which signal via dissociation of associated heterotrimeric G proteins into Gα and Gβγ subunits, have been implicated in the oocyte maturation response in many animals, either as MIH receptors, as counter-balancing regulators, and/or as receptors for upstream hormones [38].…”