Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Yantai Derui Bio-Tech Co., Ltd., Yantai, Shandong, China.
J Cell Physiol. 2021 Aug;236(8):5980-5993. doi: 10.1002/jcp.30280. Epub 2021 Jan 26.
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.
MRAP2 蛋白对黑素细胞皮质素 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平衡中起着不可或缺的作用。在几种二倍体脊椎动物中，MRAP 蛋白家族对黑素皮质素受体的相互作用和调节存在着巨大的种间差异，但在四足两栖动物非洲爪蟾（Xenopus laevis）中从未被研究过。在这里，我们进行了系统发生和基因同线性分析，以探讨 X. laevis MC4R（xlMC4R）和 MRAP2（xlMRAP2）蛋白的双重拷贝的进化方面。我们的数据表明，xlMRAPs 作为一种功能性的反平行二聚体拓扑结构直接在细胞表面与 xlMC4Rs 相互作用，药理学研究表明，在 X. laevis 中，黑素皮质素系统的调节模式具有同源特异性。
