TY - JOUR
T1 - Ring Finger Protein 11 Inhibits Melanocortin 3 and 4 Receptor Signaling
AU - Müller, Anne
AU - Niederstadt, Lars
AU - Jonas, Wenke
AU - Yi, Chun-Xia
AU - Meyer, Franziska
AU - Wiedmer, Petra
AU - Fischer, Jana
AU - Grötzinger, Carsten
AU - Schürmann, Annette
AU - Tschöp, Matthias
AU - Kleinau, Gunnar
AU - Grüters, Annette
AU - Krude, Heiko
AU - Biebermann, Heike
PY - 2016
Y1 - 2016
N2 - 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 alpha (TNF alpha)-induced NF kappa 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
AB - 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 alpha (TNF alpha)-induced NF kappa 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
U2 - https://doi.org/10.3389/fendo.2016.00109
DO - https://doi.org/10.3389/fendo.2016.00109
M3 - Article
C2 - 27551276
SN - 1664-2392
VL - 7
SP - 109
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
ER -