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- Title
Heterodimerization of Hypothalamic G-Protein-Coupled Receptors Involved in Weight Regulation.
- Authors
Rediger, Anne; Tarnow, Patrick; Bickenbach, Annika; Schaefer, Michael; Krude, Heiko; Grüters, Annette; Biebermann, Heike
- Abstract
Background: Melanocortin 3 and 4 receptors (MC3R and MC4R) are known to play an essential role in hypothalamic weight regulation. In addition to these two G-protein-coupled receptors (GPCRs), a huge number of other GPCRs are expressed in hypothalamic regions, and some of them are involved in weight regulation. So far, homodimerization was shown for a few of these receptors. Heterodimerization of unrelated receptors may have profound functional consequence but heterodimerization of GPCRs involved in weight regulation was not reported yet. Methods: A selective number of hypothalamically expressed GPCRs were cloned into a eukaryotic expression vector. Cell surface expression was demonstrated by an ELISA approach. Subcellular distribution was investigated by confocal laser microscopy. A sandwich ELISA and fluorescence resonance energy transfer (FRET) were used to determine protein-protein interaction. Results: Via sandwich ELISA and FRET approach we could demonstrate a robust interaction of the MC4R with GPR7, both of which are expressed in the hypothalamic nucleus paraventricularis. Moreover, we determined a strong interaction of MC3R with the growth hormone secretagogue receptor expressed in the nucleus arcuatus. Conclusion: Identification GPCR heterodimerization adds to the understanding of the complexity of weight regulation and may provide important information to develop therapeutic strategies to treat obesity. Copyright © 2009 S. Karger AG, Basel
- Publication
Obesity Facts: The European Journal of Obesity, 2009, Vol 2, Issue 2, p80
- ISSN
1662-4025
- Publication type
Article
- DOI
10.1159/000209862