Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes

Helgi B Schiöth,Johan Enberg,Earl T Larson,Janis Klovins,Hiroshi Kawauchi,Maja Löwgren,Robert Fredriksson,Aneta Ringholm,Tatjana Haitina,Akiyoshi Takahashi

doi:10.1186/1471-2148-7-101

Helgi B Schiöth, Johan Enberg

Open Access

https://doi.org/10.1186/1471-2148-7-101

Copy DOI

Abstract

BackgroundThe melanocortin (MC) receptors have a key role in regulating body weight and pigmentation. They belong to the rhodopsin family of G protein-coupled receptors (GPCRs). The purpose of this study was to identify ancestral MC receptors in agnathan, river lamprey.ResultsWe report cloning of two MC receptors from river lamprey. The lamprey receptors, designated MCa and MCb, showed orthology to the MC1 and MC4 receptor subtypes, respectively. The molecular clock analysis suggested that lamprey MC receptor genes were not duplicated recently and diverged from each other more than 400 MYR ago. Expression and pharmacological characterization showed that the lamprey MCa receptor was able to bind and be activated by both lamprey and human MSH peptides. The lamprey MCa receptor had relatively high affinity for ACTH derived peptides similarly to the fish MC receptors. We found that both of the lamprey MC receptors were expressed in skin, while the MCb receptor was also found in liver, heart and skeletal muscle.ConclusionThis study shows presence of MC receptors in agnathans indicating early signs of specific functions of melanocortin receptor subtypes.

Highlights

The melanocortin (MC) receptors have a key role in regulating body weight and pigmentation
We have previously demonstrated the presence of MC receptors in teleost fishes [8,9] and that the MC4 receptor plays an important role for regulation of food intake in teleosts [10,11]
Cloning of melanocortin receptors from river lamprey The degenerate PCR on genomic DNA of river lamprey resulted in two fragments of approx 400 bp

Summary

Introduction

The melanocortin (MC) receptors have a key role in regulating body weight and pigmentation. They belong to the rhodopsin family of G protein-coupled receptors (GPCRs). G protein-coupled receptors (GPCRs) are the largest superfamily of membrane proteins and serve as targets for more than 30% of all modern drugs. The rhodopsin family is the largest within the GPCR superfamily and includes the α-, β-, γ- and δ-subgroups [1]. The α group of rhodopsin GPCRs includes melanocortin (MC) receptors. BMC Evolutionary Biology 2007, 7:101 http://www.biomedcentral.com/1471-2148/7/101 signalling peptide (ASIP) and agouti related protein (AGPR) that are endogenous antagonists that regulate pigmentation and food intake through the MC1 and MC4 receptors, respectively. The MC4 receptor and the MC3 receptor, which is involved in regulating energy homeostasis, are some of the most pursued drug targets among GPCRs [7]

Objectives

Methods

Results

Discussion

Conclusion