uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Show others and affiliations
2007 (English)In: BMC Evolutionary Biology, ISSN 1471-2148, E-ISSN 1471-2148, Vol. 7, 101- p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2007. Vol. 7, 101- p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-16297DOI: 10.1186/1471-2148-7-101ISI: 000248275900001PubMedID: 17603878OAI: oai:DiVA.org:uu-16297DiVA: diva2:44068
Available from: 2008-05-16 Created: 2008-05-16 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Function, Pharmacology, Evolution and Anatomical Localization of G Protein-Coupled Receptors and Solute Carriers
Open this publication in new window or tab >>Function, Pharmacology, Evolution and Anatomical Localization of G Protein-Coupled Receptors and Solute Carriers
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The G protein-coupled receptors (GPCRs) and solute carriers (SLC) are two large families of membrane-bound proteins. The aim of this study was to characterize these two families in terms of evolution and function. The melanocortin (MC) receptors belong to the Rhodopsin family of GPCRs and we cloned the MC4 and MC5 receptors from the rainbow trout, MC3 and MC5 from the spiny dogfish and MCa and MCb from the river lamprey. Pharmacological characterization of the cloned MC receptors demonstrated higher affinity for adrenocorticotropic hormone (ACTH) compared to melanocyte stimulating hormone (MSH) peptides (alpha-, beta- and gamma-MSH). We performed expression analysis with reverse transcription PCR, which showed that the MC4 and MC5 receptors in the rainbow trout are expressed centrally as well as in peripheral tissues. The dogfish MC3 and MC5 receptors were expressed in the brain, while the lamprey MCa and MCb receptors were expressed in the periphery. An extensive tissue localization analysis was performed for the entire family of Adhesion GPCRs in the rat and mouse. Using quantitative real-time PCR (qRT-PCR) we discovered that the majority of GPCRs were expressed either specifically in the CNS or ubiquitously in the CNS and peripheral tissues. We identified all non-olfactory GPCRs in the dog and classified them into Adhesion, Frizzled, Glutamate, Rhodopsin and Secretin families. The dog GPCR repertoire seemed to be more similar to the human repertoire than to the repertoires in rodents. Solute carrier family 25 includes mitochondrial membrane transporters. Using bioinformatics techniques we identified 14 novel members of the SLC25 family, which now has 46 members. We identified orthologs of the novel SLC25 family members in yeast and performed expression analysis of 9 of them with qRT-PCR on a panel containing 30 central and peripheral tissues from the rat. To conclude, this study has expanded our knowledge of the repertoire of genes coding for membrane-bound proteins and provided information about their functional roles.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 49 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 437
National Category
Pharmacology and Toxicology
Research subject
Medicine
Identifiers
urn:nbn:se:uu:diva-99413 (URN)978-91-554-7466-9 (ISBN)
Public defence
2009-04-24, Room B41, BMC, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2009-04-03 Created: 2009-03-13 Last updated: 2009-09-04Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Haitina, Tatjana

Search in DiVA

By author/editor
Haitina, Tatjana
By organisation
Department of Neuroscience
In the same journal
BMC Evolutionary Biology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 469 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf