Heterodimerization of hypothalamic G-protein-coupled receptors involved in weight regulation

Obes Facts. 2009;2(2):80-6. doi: 10.1159/000209862. Epub 2009 Apr 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arcuate Nucleus of Hypothalamus / metabolism*
  • Body Weight / physiology*
  • COS Cells
  • Chlorocebus aethiops
  • Dimerization
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescence Resonance Energy Transfer
  • Gene Expression / physiology
  • Humans
  • Kidney / cytology
  • Obesity* / genetics
  • Obesity* / metabolism
  • Obesity* / physiopathology
  • Paraventricular Hypothalamic Nucleus / metabolism*
  • Receptor, Cannabinoid, CB1 / chemistry
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Melanocortin, Type 3 / chemistry
  • Receptor, Melanocortin, Type 3 / genetics
  • Receptor, Melanocortin, Type 3 / metabolism
  • Receptor, Melanocortin, Type 4 / chemistry
  • Receptor, Melanocortin, Type 4 / genetics
  • Receptor, Melanocortin, Type 4 / metabolism
  • Receptor, Serotonin, 5-HT1B / chemistry
  • Receptor, Serotonin, 5-HT1B / genetics
  • Receptor, Serotonin, 5-HT1B / metabolism
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, G-Protein-Coupled* / chemistry
  • Receptors, G-Protein-Coupled* / genetics
  • Receptors, G-Protein-Coupled* / metabolism
  • Receptors, Neuropeptide / chemistry
  • Receptors, Neuropeptide / genetics
  • Receptors, Neuropeptide / metabolism
  • Receptors, Neuropeptide Y / chemistry
  • Receptors, Neuropeptide Y / genetics
  • Receptors, Neuropeptide Y / metabolism
  • Receptors, Opioid, mu / chemistry
  • Receptors, Opioid, mu / genetics
  • Receptors, Opioid, mu / metabolism
  • Receptors, Peptide / chemistry
  • Receptors, Peptide / genetics
  • Receptors, Peptide / metabolism
  • Transfection

Substances

  • MC3R protein, human
  • MC4R protein, human
  • NPBWR1 protein, human
  • Receptor, Cannabinoid, CB1
  • Receptor, Melanocortin, Type 3
  • Receptor, Melanocortin, Type 4
  • Receptor, Serotonin, 5-HT1B
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Receptors, Neuropeptide Y
  • Receptors, Opioid, mu
  • Receptors, Peptide
  • glutathione receptor
  • neuropeptide Y2 receptor