Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity.
Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity.
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DOI：
10.1126/science.1233000
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发表时间：
2013-07-19
期刊：
影响因子：
--
通讯作者：
Majzoub JA
中科院分区：
文献类型：
--
作者：
Asai M;Ramachandrappa S;Joachim M;Shen Y;Zhang R;Nuthalapati N;Ramanathan V;Strochlic DE;Ferket P;Linhart K;Ho C;Novoselova TV;Garg S;Ridderstråle M;Marcus C;Hirschhorn JN;Keogh JM;O'Rahilly S;Chan LF;Clark AJ;Farooqi IS;Majzoub JA
黑皮质素受体辅助蛋白（MRAP）在体外调节黑皮质素受体的信号传导。为了研究脑表达的黑皮质素2受体辅助蛋白2（MRAP 2）的生理作用，我们对全身和脑特异性靶向缺失MRAP 2的小鼠进行了表征，这两种小鼠在年轻时都会出现严重的肥胖症。Mrap2直接与黑皮质素4受体（Mc4r）相互作用，这是一种先前与哺乳动物肥胖有关的蛋白质，它增强了Mc4r介导的第二信使环AMP的产生，这表明Mc4r信号传导的改变可能是Mrap2破坏与肥胖之间关联的一种机制。在一项对患有严重早发性肥胖症的人的研究中，我们在MRAP 2中发现了四种罕见的潜在致病性遗传变异，这表明该基因也可能有助于人类的体重调节。
Melanocortin receptor accessory proteins (MRAPs) modulate signaling of melanocortin receptors in vitro. To investigate the physiological role of brain-expressed Melanocortin 2 Receptor Accessory Protein 2 (MRAP2), we characterized mice with whole body and brain-specific targeted deletion of Mrap2, both of which develop severe obesity at a young age. Mrap2 interacts directly with Melanocortin 4 Receptor (Mc4r), a protein previously implicated in mammalian obesity, and it enhances Mc4r-mediated generation of the second messenger cyclic AMP, suggesting that alterations in Mc4r signaling may be one mechanism underlying the association between Mrap2 disruption and obesity. In a study of humans with severe, early-onset obesity, we found four rare, potentially pathogenic genetic variants in MRAP2, suggesting that the gene may also contribute to body weight regulation in humans.
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影响因子：
4.1
作者：
Hinkle PM;Sebag JA
通讯作者：
Sebag JA
DOI：
10.1073/pnas.0809918106
发表时间：
2009-04-14
影响因子：
11.1
作者：
Chan, Li F.;Webb, Tom R.;Clark, Adrian J. L.
通讯作者：
Clark, Adrian J. L.
影响因子：
3.7
作者：
Johansson LE;Johansson LM;Danielsson P;Norgren S;Johansson S;Marcus C;Ridderstråle M
通讯作者：
Ridderstråle M
影响因子：
64.5
作者：
Balthasar, N;Dalgaard, LT;Lowell, BB
通讯作者：
Lowell, BB
影响因子：
48
作者：
Tschoep, Matthias H.;Speakman, John R.;Arch, Jonathan R. S.;Auwerx, Johan;Bruening, Jens C.;Chan, Lawrence;Eckel, Robert H.;Farese, Robert V., Jr.;Galgani, Jose E.;Hambly, Catherine;Herman, Mark A.;Horvath, Tamas L.;Kahn, Barbara B.;Kozma, Sara C.;Maratos-Flier, Eleftheria;Mueller, Timo D.;Muenzberg, Heike;Pfluger, Paul T.;Plum, Leona;Reitman, Marc L.;Rahmouni, Kamal;Shulman, Gerald I.;Thomas, George;Kahn, C. Ronald;Ravussin, Eric
通讯作者：
Ravussin, Eric