Frontiers in Endocrinology (Aug 2016)

Ring finger protein 11 inhibits melanocortin 3 and 4 receptor signaling

  • Anne Müller,
  • Lars Niederstadt,
  • Wenke Jonas,
  • Wenke Jonas,
  • Chun-Xia Yi,
  • Franziska Meyer,
  • Petra Wiedmer,
  • Jana Fischer,
  • Carsten Grötzinger,
  • Annette Schürmann,
  • Annette Schürmann,
  • Matthias Tschöp,
  • Matthias Tschöp,
  • Gunnar Kleinau,
  • Annette Grüters,
  • Heiko Krude,
  • Heike Biebermann

DOI
https://doi.org/10.3389/fendo.2016.00109
Journal volume & issue
Vol. 7

Abstract

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Intact melanocortin signaling via the G protein-coupled receptors (GPCRs) melanocortin receptor 4 (MC4R) and melanocortin receptor 3 (MC3R) is crucial for body weight maintenance. So far, no connection between melanocortin signaling and hypothalamic inflammation has been reported. Using a bimolecular fluorescence complementation library screen, we identified a new interaction partner for these receptors, ring finger protein 11 (RNF11). RNF11 participates in the constitution of the A20 complex that is involved in reduction of tumor necrosis factor F-induced NFB signaling, an important pathway in hypothalamic inflammation. Mice treated with high-fat diet (HFD) for 3 days demonstrated a trend toward an increase in hypothalamic Rnf11 expression, as shown for other inflammatory markers under HFD. Furthermore, Gs-mediated signaling of MC3/4R was demonstrated to be strongly reduced to 20 - 40% by co-expression of RNF11 despite unchanged total receptor expression. Cell surface expression was not affected for MC3R but resulted in a significant reduction of MC4R to 61% by co-expression with RNF11.Mechanisms linking HFD, inflammation, and metabolism remain partially understood. In this study, a new axis between signaling of specific body weight regulating GPCRs and factors involved in hypothalamic inflammation is suggested.

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