title: Ring Finger Protein 11 Inhibits Melanocortin 3 and 4 Receptor Signaling.
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.
authors.affiliation: Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Müller
authors.affiliation: Tumor Targeting Laboratory, Department of Hepatology and Gastroenterology, Molecular Cancer Research Center (MKFZ), Charité-Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Niederstadt
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany; German Center of Diabetes Research, Neuherberg, Germany.
authors.forename: Wenke
authors.initials: W
authors.lastname: Jonas
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam , Amsterdam , Netherlands.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Yi
authors.affiliation: Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Meyer
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) , Nuthetal , Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Wiedmer
authors.affiliation: Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Fischer
authors.affiliation: Tumor Targeting Laboratory, Department of Hepatology and Gastroenterology, Molecular Cancer Research Center (MKFZ), Charité-Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Grötzinger
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany; German Center of Diabetes Research, Neuherberg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Schürmann
authors.affiliation: Institute for Diabetes and Obesity, Helmholtz Zentrum München, Germany, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany; Technische Universität München, München, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Tschöp
authors.affiliation: Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kleinau
authors.affiliation: Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Grüters
authors.affiliation: Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Krude
authors.affiliation: Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Biebermann
keywords: G protein coupled receptor; inflammation; protein complementation assay; protein network; weight regulation