Key Laboratory of Sichuan Province for Fish Conservation and Utilization in the Upper Reaches of the Yangtze River, Neijiang Normal University, Neijiang 641100, China.
College of Life Science, Neijiang Normal University, Neijiang 641100, China.
Biomolecules. 2021 Mar 23;11(3):481. doi: 10.3390/biom11030481.
The melanocortin-4 receptor (MC4R) plays an important role in the regulation of food intake and energy expenditure. Melanocortin-2 receptor accessory protein 2 (MRAP2) modulates trafficking, ligand binding, and signaling of MC4R. The Northern snakehead () is an economically important freshwater fish native to East Asia. To explore potential interaction between snakehead MC4R and MRAP2, herein we cloned snakehead and . The snakehead consisted of a 984 bp open reading frame encoding a protein of 327 amino acids, while snakehead contained a 693 bp open reading frame encoding a protein of 230 amino acids. Synteny analysis indicated that was highly conserved with similar gene arrangement, while contained two isoforms in teleost with different gene orders. Snakehead was primarily expressed in the brain, whereas was expressed in the brain and intestine. Snakehead and expression was modulated by fasting and refeeding. Further pharmacological experiments showed that the cloned snakehead MC4R was functional, capable of binding to peptide agonists and increasing intracellular cAMP production in a dose-dependent manner. Snakehead MC4R exhibited high constitutive activity. MRAP2 significantly decreased basal and agonist-stimulated cAMP signaling. These findings suggest that snakehead MC4R might be involved in energy balance regulation by interacting with MRAP2. Further studies are needed to elucidate MC4R in regulating diverse physiological processes in snakehead.
黑皮质素 4 受体（MC4R）在调节食物摄入和能量消耗方面发挥着重要作用。黑皮质素 2 受体辅助蛋白 2（MRAP2）调节 MC4R 的运输、配体结合和信号转导。北方蛇头鱼（）是一种原产于东亚的具有重要经济价值的淡水鱼类。为了探索蛇头鱼 MC4R 和 MRAP2 之间的潜在相互作用，我们在此克隆了蛇头鱼和。蛇头鱼由一个 984bp 的开放阅读框编码，编码一个 327 个氨基酸的蛋白质，而蛇头鱼包含一个 693bp 的开放阅读框，编码一个 230 个氨基酸的蛋白质。基因排列的相似性表明与高度保守，而在硬骨鱼中包含两种异构体，其基因排列不同。蛇头鱼在脑中主要表达，而在脑中也在肠中表达。禁食和再喂养调节蛇头鱼和的表达。进一步的药理学实验表明，克隆的蛇头鱼 MC4R 是功能性的，能够结合肽激动剂并以剂量依赖的方式增加细胞内 cAMP 的产生。蛇头鱼 MC4R 表现出高的组成型活性。MRAP2 显著降低了基础和激动剂刺激的 cAMP 信号。这些发现表明，蛇头鱼 MC4R 可能通过与 MRAP2 相互作用参与能量平衡的调节。需要进一步的研究来阐明 MC4R 在调节蛇头鱼多种生理过程中的作用。
