BMC evolutionary biology · 2007
Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes.
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Haitina Tatjana, Klovins Janis, Takahashi Akiyoshi, Löwgren Maja, Ringholm Aneta, Enberg Johan, Kawauchi Hiroshi, Larson Earl T, Fredriksson Robert, Schiöth Helgi B
Аннотация
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.
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.
Предметные рубрики MeSH
Adrenocorticotropic HormoneAmino Acid SequenceAnimalsBinding SitesBinding, CompetitiveCell Line, TransformedCosyntropinCyclic AMPEvolution, MolecularGene DuplicationGene LibraryHagfishesHumansMolecular Sequence DataOrgan SpecificityPeptide FragmentsPeptides, CyclicPetromyzonPhylogenyPro-OpiomelanocortinProtein BindingProtein Interaction MappingReceptor, Melanocortin, Type 1Receptor, Melanocortin, Type 4Receptors, MelanocortinRecombinant Fusion ProteinsSecond Messenger SystemsSequence AlignmentSequence Homology, Amino AcidSkinSpecies SpecificityVisceraalpha-MSHbeta-MSHgamma-MSH