MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family
MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family
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DOI：
10.1073/pnas.0809918106
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发表时间：
2009-04-14
影响因子：
11.1
通讯作者：
Clark, Adrian J. L.
中科院分区：
文献类型：
--
作者：
Chan, Li F.;Webb, Tom R.;Clark, Adrian J. L.
黑皮质素受体（MCR）家族由具有不同生理功能的5G蛋白偶联受体（MC 1 R-MC 5 R）组成。MC 2 R是下丘脑-垂体-肾上腺轴的重要组成部分，而MC 3R和MC 4 R在能量稳态中起重要作用。MC 4 R的突变是单基因肥胖症最常见的单一原因。研究这些受体向细胞膜发出信号和运输的方式对于理解与MCR功能障碍相关的疾病过程至关重要。MRAP是一种MC 2 R辅助蛋白，负责肾上腺MC 2 R的运输和功能。在这里，我们确定MRAP 2作为MRAP的一个独特的同源物，在大脑和肾上腺中表达。我们报告MRAP和MRAP 2可以与所有5个MCR交互。这种相互作用导致MC 2 R表面表达和信号传导。相比之下，MRAP和MRAP 2可以降低MC 1 R、MC 3R、MC 4 R和MC 5 R对[Nle 4，D-Phe 7] α-黑素细胞刺激激素（NDP-MSH）的响应性。总的来说，我们的数据将MRAP和MRAP 2确定为MCR家族中独特的双向调节剂。
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.