Does Kisspeptin Belong to the Proposed RF-Amide Peptide Family?

Seongsik Yun,Hubert Vaudry,Michael Furlong,Dong-Kyu Kim,Jong-Ik Hwang,Jae Young Seong

doi:10.3389/fendo.2014.00134

Seongsik Yun, Hubert Vaudry + Show 4 more

Open Access

https://doi.org/10.3389/fendo.2014.00134

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Abstract

Kisspeptin (KISS) plays a key role in regulating reproduction by binding to its receptor, GPR54. Because of the Arg-Phe (RF) sequence at its carboxyl terminus, KISS has been proposed to be a member of the RF-amide peptide family consisting of neuropeptide FF (NPFF), neuropeptide VF (NPVF), pyroglutamylated RF-amide peptide (QRFP), and prolactin-releasing hormone (PRLH). Evolutionary relationships of protein families can be determined through phylogenetic analysis. However, phylogenetic analysis among related peptide families often fails to provide sufficient information because only short mature peptide sequences from full preprohormone sequences are conserved. Considering the concept of the coevolution of peptide ligands and their cognate receptors, evolutionary relationships among related receptor families provide clues to explore relationships between their peptides. Although receptors for NPFF, NPVF, and QRFP are phylogenetically clustered together, receptors for PRLH and KISS are on different branches of the phylogenetic tree. In particular, KISS has been proposed to be a member of the KISS/galanin/spexin family based on synteny analysis and the phylogenetic relationship between their receptors. This article discusses the evolutionary history of the receptors for the proposed RF-amide peptide family and proposes that, from an evolutionary aspect, KISS has emerged from an ancestor, which is distinct from those of the other RF-amide peptides, and so should be classed separately.

Highlights

The RF-amide peptides that harbor the Arg-Phe-amide sequence in their carboxyl (C)-termini were first discovered in a species of mollusk, Macrocallista nimbosa [1]
Phylogeny of the RF-amide peptide receptor family, revealed distant relationships between PRLHR, KISSR, and the other RF-amide receptors [15, 16]. This suggests that prolactinreleasing hormone (PRLH) and KISS, at least, are likely to have originated from ancestors different from that of neuropeptide FF (NPFF), neuropeptide VF (NPVF), and QRFP
It is noteworthy that the chicken C-RF-amide peptide (PRLH2), an ohnolog of PRLH resides near neuropeptide Y (NPY), TAC1, and NPVF on the chromosomes of chickens, medaka, and tetraodon [52, 53]. These findings suggest the presence of evolutionary relationships between the NPFF family and the other RF-amide peptides QRFP and PRLH, along with non-RF-amide peptides such as NPY, TAC, and HCRT

Summary

Introduction

The RF-amide peptides that harbor the Arg-Phe-amide sequence in their carboxyl (C)-termini were first discovered in a species of mollusk, Macrocallista nimbosa [1]. The receptors for these three vertebrate RF-amide peptides, NPFFR1, NPFFR2, and QRFPR, are phylogenetically very close to each other (Figure 1), indicating an evolutionarily common origin for these receptors. This suggests that PRLH and KISS, at least, are likely to have originated from ancestors different from that of NPFF, NPVF, and QRFP.

Results

Conclusion