Pharmacological evaluation of MRAP proteins on Xenopus neural melanocortin signaling
Pharmacological evaluation of MRAP proteins on Xenopus neural melanocortin signaling
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MRAP 蛋白对非洲爪蟾神经黑皮质素信号传导的药理学评价
DOI：
10.1002/jcp.30306
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发表时间：
2021-01-31
影响因子：
5.6
通讯作者：
Zhang, Chao
中科院分区：
文献类型：
--
作者：
Tai, Xiaolu;Xue, Song;Zhang, Chao
黑素皮质素3受体（Melanocortin-3 receptor，MC 3R）和黑素皮质素4受体（melanocortin-4 receptor，MC 4 R）是两种与G蛋白偶联的神经元受体，在脊椎动物的能量平衡中起重要作用。作为黑皮质素受体的变构调节剂，黑皮质素辅助蛋白（MRAP）也参与能量稳态。MRAPs和黑皮质素信号的相互作用先前在哺乳动物和斑马鱼中显示，但在两栖动物中没有报道。两栖动物作为四足动物的基础纲，在系统发育上处于硬骨鱼类和陆生动物之间的过渡阶段。在这里，我们研究了进化保守的MC 3R，MC 4 R，和MRAPs的二倍体非洲爪蟾热带（XT-）和其他脊索动物和研究的药理学调节特性的MRAPs的神经MC 3R和MC 4 R信号。我们的研究结果表明，xtMRAP和xtMRAP 2都对激动剂（α-MSH和促肾上腺皮质激素[ACTH]）诱导的激活产生强大的增强作用，并调节xtMC 3R和xtMC 4 R的基础活性和细胞表面易位。此外，两种辅助蛋白的存在可以将xtMC 3R和xtMC 4 R转化为ACTH偏好的受体。这些结果表明，MRAP的存在表现出精细的控制神经元MC 3R和MC 4 R信号的药理活性在热带爪蟾，这是生理相关的复杂的过渡期的摄食行为在其生活史。
Melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R), two neural G protein-coupled receptors are known to be functionally critical for energy balance in vertebrates. As allosteric regulators of melanocortin receptors, melanocortin accessory proteins (MRAPs) are also involved in energy homeostasis. The interaction of MRAPs and melanocortin signaling was previously shown in mammals and zebrafish, but nothing had been reported in amphibians. As the basal class of tetrapods, amphibians occupy a phylogenetic transition between teleosts and terrestrial animals. Here we examined the evolutionary conservation of MC3R, MC4R, and MRAPs between diploid Xenopus tropicalis (xt-) and other chordates and investigated the pharmacological regulatory properties of MRAPs on the neural MC3R and MC4R signaling. Our results showed that xtMRAP and xtMRAP2 both exerted robust potentiation effect on agonist (alpha-MSH and adrenocorticotropin [ACTH]) induced activation and modulated the basal activity and cell surface translocation of xtMC3R and xtMC4R. In addition, the presence of two accessory proteins could convert xtMC3R and xtMC4R into ACTH-preferred receptors. These findings suggest that the presence of MRAPs exhibits fine control over the pharmacological activities of the neuronal MC3R and MC4R signaling in the Xenopus tropicalis, which is physiologically relevant with the complicated transition of feeding behaviors during their life history.