MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family

被引：188

作者：

Chan, Li F. ^{[1
]}

Webb, Tom R. ^{[1
]}

Chung, Teng-Teng ^{[1
]}

Meimaridou, Eirini ^{[1
]}

Cooray, Sadani N. ^{[1
]}

Guasti, Leonardo ^{[1
]}

Chapple, J. Paul ^{[1
]}

Egertova, Michaela ^{[2
]}

Elphick, Maurice R. ^{[2
]}

Cheetham, Michael E. ^{[3
]}

Metherell, Louise A. ^{[1
]}

Clark, Adrian J. L. ^{[1
]}

机构：

[1] Queen Marys Univ London, Ctr Endocrinol, St Bartholomews & Royal London Sch Med & Dent, London EC1M 6BQ, England

[2] Univ London, Sch Biol & Chem Sci, London E1 4NS, England

[3] UCL, Inst Ophthalmol, Div Mol & Cellular Neurosci, London EC1V 9EL, England

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 15期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

GPCR accessory proteins; receptor signalling; receptor trafficking; FAT MASS; OBESITY; MOUSE; MC4R; EXPRESSION; MUTATIONS; CELLS; GENE;

D O I：

10.1073/pnas.0809918106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：6146 / 6151

页数：6

共 21 条

[1]

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