| Literature DB >> 19329486 |
Li F Chan1, Tom R Webb, Teng-Teng Chung, Eirini Meimaridou, Sadani N Cooray, Leonardo Guasti, J Paul Chapple, Michaela Egertová, Maurice R Elphick, Michael E Cheetham, Louise A Metherell, Adrian J L Clark.
Abstract
The melanocortin receptor (MCR) family consists of 5 G protein-coupled receptors (MC1R-MC5R) with diverse physiologic roles. MC2R is a critical component of the hypothalamic-pituitary-adrenal axis, whereas MC3R and MC4R have an essential role in energy homeostasis. Mutations in MC4R are the single most common cause of monogenic obesity. Investigating the way in which these receptors signal and traffic to the cell membrane is vital in understanding disease processes related to MCR dysfunction. MRAP is an MC2R accessory protein, responsible for adrenal MC2R trafficking and function. Here we identify MRAP2 as a unique homologue of MRAP, expressed in brain and the adrenal gland. We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). Collectively, our data identify MRAP and MRAP2 as unique bidirectional regulators of the MCR family.Entities:
Mesh：
Substances：
Year: 2009 PMID： 19329486 PMCID： PMC2661846 DOI： 10.1073/pnas.0809918106
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205