Regions of MRAP2 required for the inhibition of orexin and prokineticin receptor signaling

Alix A J Rouault; Abigail A Lee; Julien A Sebag

doi:10.1016/j.bbamcr.2017.09.008

Regions of MRAP2 required for the inhibition of orexin and prokineticin receptor signaling

Biochim Biophys Acta Mol Cell Res. 2017 Dec;1864(12):2322-2329. doi: 10.1016/j.bbamcr.2017.09.008. Epub 2017 Sep 20.

Authors

Alix A J Rouault¹, Abigail A Lee¹, Julien A Sebag²

Affiliations

¹ Department of Molecular Physiology and Biophysics, Carver College of Medicine, Fraternal Order of Eagle Diabetes Research Center, Pappajohn Biomedical Institute, University of Iowa, Iowa City, United States.
² Department of Molecular Physiology and Biophysics, Carver College of Medicine, Fraternal Order of Eagle Diabetes Research Center, Pappajohn Biomedical Institute, University of Iowa, Iowa City, United States. Electronic address: Julien-sebag@uiowa.edu.

PMID: 28939058
DOI: 10.1016/j.bbamcr.2017.09.008

Abstract

The Melanocortin Receptor Accessory Protein 2 (MRAP2) regulates the activity of several GPCRs involved in the control of food intake and energy expenditure. While MRAP2 was originally thought to exclusively interact with melanocortin receptors we have recently shown that it interacts with and inhibits the trafficking and signaling of the prokineticin receptor 1 (PKR1). In this study we demonstrate a new role of MRAP2 in the regulation of the orexin receptor 1 (OX1R) and identify the specific regions of MRAP2 required for the regulation of OX1R and PKR1. Importantly, like MC4R and PKRs, OX1R is predominately expressed in the brain where it regulates food intake. By demonstrating that MRAP2 modulates the activity of OX1R we further establish the critical role of MRAP2 in the control of energy homeostasis.

Keywords: Cell signaling; GPCR; MRAP; MRAP2; OX1R; Orexin; PKR1; Prokineticin; Receptor regulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Animals
CHO Cells
Calcium Signaling / genetics
Carrier Proteins / genetics
Carrier Proteins / metabolism*
Cricetulus
Eating / genetics*
Energy Metabolism / genetics
Humans
Orexin Receptors / genetics*
Orexins / genetics
Orexins / metabolism
Receptors, G-Protein-Coupled / genetics*
Signal Transduction
Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / genetics
Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / metabolism

Substances

Adaptor Proteins, Signal Transducing
Carrier Proteins
HCRTR1 protein, human
MRAP2 protein, human
Orexin Receptors
Orexins
PROKR1 protein, human
Receptors, G-Protein-Coupled
Vascular Endothelial Growth Factor, Endocrine-Gland-Derived