Physiological modulation of melanocortin‐4 receptor (MC4R) signaling by MRAP2 proteins plays an indispensable role in appetite control and energy homeostasis in the central nervous system. Great interspecies differences of the interaction and regulation of melanocortin receptors by MRAP protein family have been reported in several diploid vertebrates but never been investigated in the tetrapod amphibian Xenopus laevis. Here, we performed phylogenetic and synteny‐based analyses to explore the evolutionary aspects of dual copies of X. laevis MC4R (xlMC4R) and MRAP2 (xlMRAP2) proteins. Our data showed that xlMRAPs directly interacted with xlMC4Rs on the cell surface as a functional antiparallel dimeric topology and pharmacological studies suggested a homology specific regulatory pattern of the melanocortin system in X. laevis.

中文翻译：

---

非洲爪蟾中黑色皮质素受体辅助蛋白对双重黑色皮质素 4 受体信号的药理学调节

MRAP2 蛋白对黑皮质素 4 受体 (MC4R) 信号的生理调节在中枢神经系统的食欲控制和能量稳态中起着不可或缺的作用。MRAP 蛋白家族对黑皮质素受体的相互作用和调节的巨大种间差异已在几种二倍体脊椎动物中报道，但从未在四足两栖动物非洲爪蟾中进行过研究。在这里，我们进行了系统发育和基于同线性的分析，以探索X. laevis双拷贝的进化方面MC4R (xlMC4R) 和 MRAP2 (xlMRAP2) 蛋白。我们的数据表明，xlMRAPs直接相互作用与细胞表面上xlMC4Rs作为官能反平行二聚体的拓扑结构和药理学研究表明在黑皮质素系统的同源性特异性调节图案非洲爪蟾。