The Melanocortin Receptor Accessory Protein 2 promotes food intake through inhibition of the Prokineticin Receptor-1
The Melanocortin Receptor Accessory Protein 2 promotes food intake through inhibition of the Prokineticin Receptor-1
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DOI：
10.7554/elife.12397
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发表时间：
2016-02-01
期刊：
影响因子：
7.7
通讯作者：
Sebag, Julien A.
中科院分区：
文献类型：
--
作者：
Chaly, Anna L.;Srisai, Dollada;Sebag, Julien A.
黑皮质素受体辅助蛋白2（MRAP 2）是能量稳态的重要调节剂，其缺失导致啮齿动物严重肥胖。MRAP 2部分通过增强MC4R介导其作用，然而，很明显，MRAP 2在不表达MC4R的组织中表达，并且MRAP 2的缺失不重现Mc4r KO小鼠的表型。因此，我们假设参与能量稳态控制的其他GPCR可能受MRAP 2调控。在这项研究中，我们确定PKR1作为第一个nonmelanocortin GPCR的MRAP 2调节。我们发现，MRAP 2显着和特异性抑制PKR1信号。我们还表明，PKR1和MRAP 2共定位于神经元和MRAP 2 KO小鼠是超敏感的PKR1刺激。这项研究不仅确定了MRAP 2的新伙伴，而且还确定了MRAP 2调节能量稳态的新途径。
The Melanocortin Receptor Accessory Protein 2 (MRAP2) is an important regulator of energy homeostasis and its loss causes severe obesity in rodents. MRAP2 mediates its action in part through the potentiation of the MC4R, however, it is clear that MRAP2 is expressed in tissues that do not express MC4R, and that the deletion of MRAP2 does not recapitulate the phenotype of Mc4r KO mice. Consequently, we hypothesized that other GPCRs involved in the control of energy homeostasis are likely to be regulated by MRAP2. In this study we identified PKR1 as the first nonmelanocortin GPCR to be regulated by MRAP2. We show that MRAP2 significantly and specifically inhibits PKR1 signaling. We also demonstrate that PKR1 and MRAP2 co-localize in neurons and that Mrap2 KO mice are hypersensitive to PKR1 stimulation. This study not only identifies new partners of MRAP2 but also a new pathway through which MRAP2 regulates energy homeostasis.