Ring finger protein 11 inhibits melanocortin 3 and 4 receptor signaling
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 bimolecula...
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doaj-96d82d05fe2d4aada5986c9637c38bf62020-11-24T23:32:25ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922016-08-01710.3389/fendo.2016.00109209518Ring finger protein 11 inhibits melanocortin 3 and 4 receptor signalingAnne Müller0Lars Niederstadt1Wenke Jonas2Wenke Jonas3Chun-Xia Yi4Franziska Meyer5Petra Wiedmer6Jana Fischer7Carsten Grötzinger8Annette Schürmann9Annette Schürmann10Matthias Tschöp11Matthias Tschöp12Gunnar Kleinau13Annette Grüters14Heiko Krude15Heike Biebermann16Charité-Universitätsmedizin BerlinCharité-Universitätsmedizin BerlinGerman Institute of Human Nutrition Potsdam-Rehbruecke (DIfE)German Center of Diabetes ResearchUniversity of Amsterdam, Academic Medical Center (AMC)Charité-Universitätsmedizin BerlinGerman Institute of Human Nutrition Potsdam-Rehbruecke (DIfE)Charité-Universitätsmedizin BerlinCharité-Universitätsmedizin BerlinGerman Institute of Human Nutrition Potsdam-Rehbruecke (DIfE)German Center of Diabetes ResearchHelmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH)Technische Universität MünchenCharité-Universitätsmedizin BerlinCharité-Universitätsmedizin BerlinCharité-Universitätsmedizin BerlinCharité-Universitätsmedizin BerlinIntact 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 NFB 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.http://journal.frontiersin.org/Journal/10.3389/fendo.2016.00109/fullInflammationG protein coupled receptorprotein networkweight regulationProtein complementation assay |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Ring finger protein 11 inhibits melanocortin 3 and 4 receptor signaling Frontiers in Endocrinology Inflammation G protein coupled receptor protein network weight regulation Protein complementation assay |
author_facet |
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 |
author_sort |
Anne Müller |
title |
Ring finger protein 11 inhibits melanocortin 3 and 4 receptor signaling |
title_short |
Ring finger protein 11 inhibits melanocortin 3 and 4 receptor signaling |
title_full |
Ring finger protein 11 inhibits melanocortin 3 and 4 receptor signaling |
title_fullStr |
Ring finger protein 11 inhibits melanocortin 3 and 4 receptor signaling |
title_full_unstemmed |
Ring finger protein 11 inhibits melanocortin 3 and 4 receptor signaling |
title_sort |
ring finger protein 11 inhibits melanocortin 3 and 4 receptor signaling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Endocrinology |
issn |
1664-2392 |
publishDate |
2016-08-01 |
description |
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 NFB 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. |
topic |
Inflammation G protein coupled receptor protein network weight regulation Protein complementation assay |
url |
http://journal.frontiersin.org/Journal/10.3389/fendo.2016.00109/full |
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