Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Science. 2013 Jul 19;341(6143):278-81. doi: 10.1126/science.1232995.
The melanocortin-4 receptor (MC4R) is essential for control of energy homeostasis in vertebrates. MC4R interacts with melanocortin receptor accessory protein 2 (MRAP2) in vitro, but its functions in vivo are unknown. We found that MRAP2a, a larval form, stimulates growth of zebrafish by specifically blocking the action of MC4R. In cell culture, this protein binds MC4R and reduces the ability of the receptor to bind its ligand, α-melanocyte-stimulating hormone (α-MSH). A paralog, MRAP2b, expressed later in development, also binds MC4R but increases ligand sensitivity. Thus, MRAP2 proteins allow for developmental control of MC4R activity, with MRAP2a blocking its function and stimulating growth during larval development, whereas MRAP2b enhances responsiveness to α-MSH once the zebrafish begins feeding, thus increasing the capacity for regulated feeding and growth.
黑皮质素 4 受体 (MC4R) 是脊椎动物能量平衡控制的必需物质。MC4R 在体外与黑皮质素受体辅助蛋白 2 (MRAP2) 相互作用，但它在体内的功能尚不清楚。我们发现，幼虫形式的 MRAP2a 通过特异性阻断 MC4R 的作用来刺激斑马鱼的生长。在细胞培养中，这种蛋白质与 MC4R 结合，降低了受体与配体 α-促黑素细胞激素 (α-MSH) 结合的能力。一个在发育后期表达的同源物，MRAP2b，也与 MC4R 结合，但增加了配体的敏感性。因此，MRAP2 蛋白允许 MC4R 活性的发育控制，MRAP2a 阻断其功能并在幼虫发育期间刺激生长，而 MRAP2b 增强了对 α-MSH 的反应性，一旦斑马鱼开始进食，从而增加了调节进食和生长的能力。
