Invertebrate Gonadotropin-Releasing Hormone-Related Peptides and Their Receptors: An Update

Abstract

Gonadotropin-releasing hormones (GnRHs) play pivotal roles in reproductive functions via the hypothalamus, pituitary, and gonad axis, namely, HPG axis in vertebrates. GnRHs and their receptors (GnRHRs) are likely to be conserved in invertebrate deuterostomes and lophotrochozoans. All vertebrate and urochordate GnRHs are composed of 10 amino acids, whereas protostome, echinoderm, and amphioxus GnRH-like peptides are 11- or 12-residue peptide containing two amino acids after an N-terminal pyro-Glu. In urochordates, Halocynthia roretzi GnRH gene encodes two GnRH peptide sequences, whereas two GnRH genes encode three different GnRH peptides in Ciona intestinalis. These findings indicate the species-specific diversification of GnRHs. Intriguingly, the major signaling pathway for GnRHRs is intracellular Ca2+ mobilization in chordates, echinoderms, and protostomes, whereas Ciona GnRHRs (Ci-GnRHRs) are endowed with multiple GnRHergic cAMP production pathways in a ligand-selective manner. Moreover, the ligand-specific modulation of signal transduction via heterodimerization among Ci-GnRHR paralogs suggests the species-specific development of fine-tuning of gonadal functions in ascidians. Echinoderm GnRH-like peptides show high sequence differences compared to those of protostome counterparts, leading to the difficulty in classification of peptides and receptors. These findings also show both the diversity and conservation of GnRH signaling systems in invertebrates. The lack of the HPG axis in invertebrates indicates that biological functions of GnRHs are not release of gonadotropins in current invertebrates and common ancestors of vertebrates and invertebrates. To date, authentic or putative GnRHRs have been characterized from various echinoderms and protostomes as well as chordates and the mRNAs have been found to be distributed not only reproductive organs but also other tissues. Collectively, these findings further support the notion that invertebrate GnRHs have biological roles other than the regulation of reproductive functions. Moreover, recent molecular phylogenetic analysis suggests that adipokinetic hormone (AKH), corazonin (CRZ), and AKH/CRZ-related peptide (ACP) belong to the GnRH superfamily but has led to the different classifications of these peptides and receptors using different datasets including the number of sequences and structural domains. In this review, we provide current knowledge of, and perspectives in, molecular basis and evolutionary aspects of the GnRH, AKH, CRZ, and ACP.

Functional Characterization and Signaling Systems of Corazonin and Red Pigment Concentrating Hormone in the Green Shore Crab, Carcinus maenas

“…The recent important findings that GnRH and CRZ signaling pathways (both peptides and receptors) are found in echinoderms (Tian et al, 2016 ); are of particular significance in supporting this hypothesis. It is believed that a second gene duplication in a common ancestor to the Arthropoda gave rise to AKH- and ACP-type receptors, whilst CRZ-type receptors have been lost in multiple (vertebrate) lineages (Reviews: Sakai et al, 2017 ; Zandawala et al, 2017 ). The evolution, emergence (and loss) of members of the AKH/CRZ/ACP peptide and receptor superfamily in lophotrochozoans and arthropods have been recently reviewed (Hauser and Grimmelikhuijzen, 2014 ; Li et al, 2016 ).…”

Comprehensive analysis of differential expression profiles via transcriptome sequencing in SH-SY5Y cells infected with CV-A16

“…control of reproductive functions in all vertebrate species [28]. However, the role of abnormalities in this pathway in CV-A16 infection is unknown.…”

Evolutionary Viewpoint on GnRH (gonadotropin-releasing hormone) in Chordata - Amino Acid and Nucleic Acid Sequences

“…GnRH was first isolated from the hypothalamus of mammals in early 1970s ( Baba et al, 1971 ; Matsuo et al, 1971 ; Schally et al, 1971 ). It was then identified in most animals of Chordata and subsequently in invertebrates ( Millar, 2005 ; Roch et al, 2011 ; Hasunuma & Terakado, 2013 ; Sakai et al, 2017 ). The functional hypothalamic GnRH found in vertebrates is a decapeptide, consisting of 10 amino acids ( Fig.…”