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Müller A, Niederstadt L, Jonas W, et al. Ring Finger Protein 11 Inhibits Melanocortin 3 and 4 Receptor Signaling. Front Endocrinol (Lausanne). 2016;7:109doi: 10.3389/fendo.2016.00109.
Müller, A., Niederstadt, L., Jonas, W., Yi, C. X., Meyer, F., Wiedmer, P., Fischer, J., Grötzinger, C., Schürmann, A., Tschöp, M., Kleinau, G., Grüters, A., Krude, H., & Biebermann, H. (2016). Ring Finger Protein 11 Inhibits Melanocortin 3 and 4 Receptor Signaling. Frontiers in endocrinology, 7109. https://doi.org/10.3389/fendo.2016.00109
Müller, Anne, et al. "Ring Finger Protein 11 Inhibits Melanocortin 3 and 4 Receptor Signaling." Frontiers in endocrinology vol. 7 (2016): 109. doi: https://doi.org/10.3389/fendo.2016.00109
Müller A, Niederstadt L, Jonas W, Yi CX, Meyer F, Wiedmer P, Fischer J, Grötzinger C, Schürmann A, Tschöp M, Kleinau G, Grüters A, Krude H, Biebermann H. Ring Finger Protein 11 Inhibits Melanocortin 3 and 4 Receptor Signaling. Front Endocrinol (Lausanne). 2016 Aug 08;7:109. doi: 10.3389/fendo.2016.00109. eCollection 2016. PMID: 27551276; PMCID: PMC4976663.
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Front Endocrinol (Lausanne). 2016 Aug 08;7:109. doi: 10.3389/fendo.2016.00109. eCollection 2016.

Ring Finger Protein 11 Inhibits Melanocortin 3 and 4 Receptor Signaling.

Frontiers in endocrinology

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

Affiliations

  1. Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin , Germany.
  2. Tumor Targeting Laboratory, Department of Hepatology and Gastroenterology, Molecular Cancer Research Center (MKFZ), Charité-Universitätsmedizin Berlin , Berlin , Germany.
  3. Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany; German Center of Diabetes Research, Neuherberg, Germany.
  4. Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam , Amsterdam , Netherlands.
  5. Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin , Germany.
  6. Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) , Nuthetal , Germany.
  7. Institute for Diabetes and Obesity, Helmholtz Zentrum München, Germany, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany; Technische Universität München, München, Germany.

PMID: 27551276 PMCID: PMC4976663 DOI: 10.3389/fendo.2016.00109

Abstract

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 α (TNFα)-induced NFκB 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.

Keywords: G protein coupled receptor; inflammation; protein complementation assay; protein network; weight regulation

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