Differential activation of kiss receptors by Kiss1 and Kiss2 peptides in the sea bass

Abstract

Two forms of kiss gene (kiss1 and kiss2) have been described in the teleost sea bass. This study assesses the cloning and characterization of two Kiss receptor genes, namely kissr2 and kissr3 (known as gpr54-1b and gpr54-2b, respectively), and their signal transduction pathways in response to Kiss1 and Kiss2 peptides. Phylogenetic and synteny analyses indicate that these paralogs originated by duplication of an ancestral gene before teleost specific duplication. The kissr2 and kissr3 mRNAs encode proteins of 368 and 378 amino acids, respectively, and share 53.1% similarity in amino acid sequences. In silico analysis of the putative promoter regions of the sea bass Kiss receptor genes revealed conserved flanking regulatory sequences among teleosts. Both kissr2 and kissr3 are predominantly expressed in brain and gonads of sea bass, medaka and zebrafish. In the testis, the expression levels of sea bass kisspeptins and Kiss receptors point to a significant variation during the reproductive cycle. In vitro functional analyses revealed that sea bass Kiss receptor signals are transduced both via the protein kinase C and protein kinase A pathway. Synthetic sea bass Kiss1-15 and Kiss2-12 peptides activated Kiss receptors with different potencies, indicating a differential ligand selectivity. Our data suggest that Kissr2 and Kissr3 have a preference for Kiss1 and Kiss2 peptides, respectively, thus providing the basis for future studies aimed at establishing their physiologic roles in sea bass. . To date, a single ligand (Kiss) and receptor (Gpr54 or Kissr) have been demonstrated to exist in placental mammals (human, opossum) and reptiles, while mammalian monotrems (platypus) possess two forms of Kiss and Kissr genes. Contrasting situations are found in other tetrapodes, such as amphibians, which have three kiss and kissr genes, whereas the kisspeptin system is absent in birds, although a recent investigation into the kisspeptin system in avian lineages provides molecular evidence of the presence of a kiss2-like gene that degenerated and lost its function (Pasquier et al. 2014b). All in all, advances in genome sequencing and comparative genomics in several groups occupying relevant phylogenetic positions have led to the identification of four kissr and three kiss genes in the coelacanth (Sarcopterygian), while in teleosts at least one kiss and kissr is known to be present in all the species investigated to date. Nevertheless, a second gene for kisspeptin and its receptor has been observed in the genomes of other fish species (Biran et al. 2008, Akazome et al. 2010, Oakley et al. 2010, Um et al. 2010, Zohar et al. 2010, Kim et al. 2012, Pasquier et al. 2012a,b, Tena-Sempere et al. 2012. So far, the occurrence of three kissr and two kiss paralogous genes has been reported in an early group of teleosts, the Elopomorphs (European eel, Anguilla anguilla) (Pasquier et al. 2012a,b). In the spotted gar, Lepisosteus oculatus (Actinopterygian, Ginglymode), four kissr and two kiss have been identified, while four kiss but n...

Eel Kisspeptins: Identification, Functional Activity, and Inhibition on both Pituitary LH and GnRH Receptor Expression

“…In other teleosts possessing two kisspeptin genes, different situations have been reported. In some species, both kisspeptins are detected in the gonads [medaka and zebrafish ( 42 , 53 ); sea bass ( 60 ); rohu ( 45 ); and Catla catla ( 46 , 47 )]. In contrast, in the chub mackerel, Kiss1 is expressed in the gonads of both sexes, while Kiss2 expression is not detected ( 44 ), whereas in the pejerrey, expression of both genes is very low in the gonads ( 48 ).…”

“…Eel Kp1(15) exhibited about the same potency to activate rat KissR-1 than eel Kp1(10), which is identical to rat Kp1(10). Interestingly, eel Kiss2-derived peptides were also able to activate rat KissR-1, as zebrafish ( 59 ) and sea bass ( 60 ) peptides did with human KissR-1.…”

“…Zebrafish Kiss peptides are also highly efficient for activating mammalian (human) KissR-1 in COS-7 cells [zebrafish Kp1(10) ( 41 )] and in CV-1 cells [zebrafish Kp1(15), Kp2(10), and Kp2(12) ( 59 )]. Similarly, in CHO cells, sea bass Kiss peptides [sea bass Kp1(10), Kp2(10), Kp1(15), and Kp2(12)] can efficiently activate human KissR-1, while, in the case of mouse KissR-1, sea bass Kp2(10) is not able to induce any activation ( 60 ).…”

Conformational analysis of a synthetic fish kisspeptin 1 peptide in membrane mimicking environments

“…Unlike mammals, long kiss peptides are reported to be more potent activators of kisspeptin receptors in several fish species such as zebrafish ( Danio rerio ) [ 14 ], striped bass ( Morone saxatilis ) [ 15 ], chub mackerel ( Scomber japonicus ) [ 16 ], medaka ( Oryzias latipes ) [ 17 ] and, European sea bass ( Dicentrarchus labrax ) [ 18 ]. Moreover, majority of the fish kisspeptin 1 have -RY-NH 2 motif at C-terminal as compared to -RF-NH 2 motif reported in most mammals [ 14 ].…”

Actions of sex steroids on kisspeptin expression and other reproduction-related genes in the brain of the teleost fish european sea bass

“…Since the reproductive physiology of European sea bass (Dicentrarchus labrax, Linnaeus) is well documented (Carrillo et al, 1995, this species has emerged as an interesting teleost model to investigate the differential involvement of the two kisspeptin systems in controlling fish reproduction (Alvarado et al, 2013;Escobar et al, 2013a,b;Felip et al, 2009Felip et al, , 2015Migaud et al, 2012). This species exhibits a clear stimulation of gonadotropin release following systemic kisspeptin administration , and more recently, intracerebroventricular injections of Kiss2 have demonstrated the involvement of this peptide in neuroendocrine regulation of gonadotroph activity .…”