Faculty Collaboration Database

MRAP2 regulates ghrelin receptor signaling and hunger sensing. Nat Commun 2017 Sep 28;8(1):713

Date

09/30/2017

Pubmed ID

28959025

Pubmed Central ID

PMC5620068

DOI

10.1038/s41467-017-00747-6

Scopus ID

2-s2.0-85030105001 (requires institutional sign-in at Scopus site)   52 Citations

Abstract

Ghrelin is the only known circulating orexigenic hormone. It is primarily secreted by the stomach and acts at its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), in the hypothalamus to signal hunger and promote food intake. The melanocortin receptor accessory protein 2 (MRAP2) was previously shown to regulate energy homeostasis through the modulation of the activity of the melanocortin-4 receptor and prokineticin receptors. In this study we identify MRAP2 as a partner of ghrelin-GHSR1a signaling. We show that MRAP2 interacts with GHSR1a and potentiates ghrelin-stimulated signaling both in vitro and in vivo. We demonstrate that in the absence of MRAP2, fasting fails to activate agouti-related protein neurons. In addition, we show that the orexigenic effect of ghrelin is lost in mice lacking MRAP2. Our results suggest that MRAP2 is an important modulator of the energy homeostasis machinery that operates through the regulation of multiple GPCRs throughout the hypothalamus.Melanocortin receptor accessory protein 2 (MRAP2) is an adaptor protein that contributes to melanocortin-4 receptor and prokineticin receptor 1 signalling. Here the authors show that MRAP2 also regulates ghrelin receptor signalling in the hypothalamus and starvation sensing in mice.

Author List

Srisai D, Yin TC, Lee AA, Rouault AAJ, Pearson NA, Grobe JL, Sebag JA

Author

Justin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adaptor Proteins, Signal Transducing
Animals
Eating
Energy Metabolism
Ghrelin
Homeostasis
Hunger
Hypothalamus
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptor Activity-Modifying Proteins
Receptor, Melanocortin, Type 4
Receptors, Ghrelin
Signal Transduction