Relaxin-like Gonad-Stimulating Peptides in Asteroidea

Abstract

Starfish relaxin-like gonad-stimulating peptide (RGP) is the first identified peptide hormone with gonadotropin-like activity in invertebrates. RGP is a heterodimeric peptide, comprising A and B chains with disulfide cross-linkages. Although RGP had been named a gonad-stimulating substance (GSS), the purified peptide is a member of relaxin-type peptide family. Thus, GSS was renamed as RGP. The cDNA of RGP encodes not only the A and B chains, but also signal and C-peptides. After the rgp gene is translated as a precursor, mature RGP is produced by eliminating the signal and C-peptides. Hitherto, twenty-four RGP orthologs have been identified or predicted from starfish in the orders Valvatida, Forcipulatida, Paxillosida, Spinulosida, and Velatida. The molecular evolution of the RGP family is in good accordance with the phylogenetic taxonomy in Asteroidea. Recently, another relaxin-like peptide with gonadotropin-like activity, RLP2, was found in starfish. RGP is mainly present in the radial nerve cords and circumoral nerve rings, but also in the arm tips, the gonoducts, and the coelomocytes. RGP acts on ovarian follicle cells and testicular interstitial cells to induce the production of 1-methyladenine (1-MeAde), a starfish maturation-inducing hormone. RGP-induced 1-MeAde production is accompanied by an increase in intracellular cyclic AMP levels. This suggests that the receptor for RGP (RGPR) is a G protein-coupled receptor (GPCR). Two types of GPCRs, RGPR1 and RGPR2, have been postulated as candidates. Furthermore, 1-MeAde produced by RGP not only induces oocyte maturation, but also induces gamete shedding, possibly by stimulating the secretion of acetylcholine in the ovaries and testes. Thus, RGP plays an important role in starfish reproduction, but its secretion mechanism is still unknown. It has also been revealed that RGP is found in the peripheral adhesive papillae of the brachiolaria arms. However, gonads are not developed in the larvae before metamorphosis. It may be possible to discover new physiological functions of RGP other than gonadotropin-like activity.

The Current Situation and Development Prospect of Whole-Genome Screening

“…The overexpression of cDNA is widely used to screen gene targets and study functional genomics. In genome-scale genetic screening, people screen gene targets by constructing cDNA libraries, overexpression or introducing foreign genes, and observing phenotypic changes [ 20 , 21 , 22 ]. Since overexpression can significantly increase the expression level of specific genes, it is beneficial to directly observe the corresponding cellular superficial changes after gene expression.…”

Gonadotropic activity of a second relaxin-type peptide in starfish

“…Thus, mature Ppe-RGP is produced from its precursor protein by elimination of the signal peptide and C-peptide and formation of intra-chain and inter-chain disulfide bridges within and between the A-and Bchains. Orthologs of PpeRGP have also been identified in other starfish, including species belonging to the orders Valvatida, Forcipulatida, Paxillosida, Platyasteroidea, Spinulosida, and Valatida (Mita, 2013(Mita, , 2016Semmens et al, 2016;Lin et al, 2017;Smith et al, 2017;Mita et al, 2015Mita et al, , 2020aMita et al, , 2022Katayama and Mita, 2023;Mita, 2023).…”

“…More specifically, phylogenetic sequence analysis incorporating precursor sequences from vertebrates and protostome invertebrates revealed that the starfish peptide is a member of the relaxin-type peptide family (Mita et al, 2009(Mita et al, , 2015Lin et al, 2017). Hence, GSS was renamed relaxin-like gonad-stimulating peptide (RGP) (Mita, 2016(Mita, , 2019(Mita, , 2023. Furthermore, P. pectinifera RGP (Ppe-RGP) was the first gonadotropic hormone that triggers final gamete maturation and ovulation to be identified in an invertebrate.…”

“…Recently, the precursor of a second relaxin-like peptide (RLP2) was identified in the common European starfish Asterias rubens (Aru-RLP2) by analysis of neural transcriptome sequence data (Semmens et al, 2016). Furthermore, analysis of the Sequence Read Archive (SRA) has revealed the occurrence of precursors of Aru-RLP2-like peptides in other starfish species (Veenstra, 2021;Mita 2023). It was also reported that RGP/RLP2-type precursors are closely related to IGF-type precursors (Veenstra, 2021), but this interpretation of an evolutionary relationship was influenced by omission of vertebrate and protostome relaxintype precursors from the phylogenetic analysis performed.…”