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

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RESEARCH PRODUCT

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

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

subject

Pro-Opiomelanocortin Second Messenger Systems Gene Duplication Protein Interaction Mapping Cyclic AMP Petromyzon Receptor Phylogeny Cell Line Transformed Skin Genetics biology Receptors Melanocortin Melanocortin 3 receptor Cell biology Organ Specificity Rhodopsin Receptor Melanocortin Type 4 Hagfishes Melanocortin Receptor Melanocortin Type 1 Protein Binding Research Article Evolution Recombinant Fusion Proteins Molecular Sequence Data Binding Competitive Peptides Cyclic Evolution Molecular gamma-MSH Adrenocorticotropic Hormone Species Specificity Melanocortin receptor beta-MSH QH359-425 Animals Humans Amino Acid Sequence Ecology Evolution Behavior and Systematics Gene Library G protein-coupled receptor Binding Sites Sequence Homology Amino Acid Fugu Lamprey biology.organism_classification Peptide Fragments Viscera alpha-MSH biology.protein Cosyntropin Sequence Alignment human activities

description

Abstract Background 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). The purpose of this study was to identify ancestral MC receptors in agnathan, river lamprey. Results We 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. Conclusion This study shows presence of MC receptors in agnathans indicating early signs of specific functions of melanocortin receptor subtypes.

year	journal	country	edition	language
2007-01-12	BMC Evolutionary Biology

10.1186/1471-2148-7-101 http://dx.doi.org/10.1186/1471-2148-7-101