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Pharmacological modulation of the cAMP signaling of two isoforms of melanocortin-3 receptor by melanocortin receptor accessory proteins in the tetrapod Xenopus laevis

机译:三叶素受体辅助蛋白在三藏素受体辅助蛋白在四射素受体辅助蛋白的两种同种型CAMP信号的药理调制<斜体切换=“是”> Xenopus Laevis

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As a member of the seven-transmembrane rhodopsin-like G protein-coupled receptor superfamily, the melanocortin-3 receptor (MC3R) is vital for the regulation of energy homeostasis and rhythms synchronizing in mammals, and its pharmacological effect could be directly influenced by the presence of melanocortin receptor accessory proteins (MRAPs), MRAP1 and MRAP2. The tetrapod amphibian Xenopus laevis (xl) retains higher duplicated genome than extant teleosts and serves as an ideal model system for embryonic development and physiological studies. However, the melanocortin system of the Xenopus laevis has not yet been thoroughly evaluated. In this work, we performed sequence alignment, phylogenetic tree, and synteny analysis of two xlMC3Rs. Co-immunoprecipitation and immunofluorescence assay further confirmed the co-localization and in vitro interaction of xlMC3Rs with xlMRAPs on the plasma membrane. Our results demonstrated that xlMRAP2.L/S could improve α-MSH-stimulated xlMC3Rs signaling and suppress their surface expression. Moreover, xlMC3R.L showed a similar profile on the ligands and surface expression in the presence of xlMRAP1.L. Overall, the distinct pharmacological modulation of xlMC3R.L and xlMC3R.S by dual MRAP2 proteins elucidated the functional consistency of melanocortin system during genomic duplication of tetrapod vertebrates.
机译:作为七跨膜罗霉素样G蛋白偶联受体超家族的成员,黑色激素-3受体(MC3R)对于调节能源稳态和哺乳动物同步的节奏至关重要,其药理效应可以直接影响黑色素体受体辅助蛋白(MRAP),MRAP1和MRAP2的存在。 Tetrapod Amphibian Xenopus Laevis(XL)保留更高的重复基因组,而不是远端紧邻,并用作胚胎发育和生理学研究的理想模型系统。然而,Xenopus Laevis的Melanocortin系统尚未彻底评估。在这项工作中,我们对两个XLMC3RS进行了序列对准,系统发育树和同步分析。共免疫沉淀和免疫荧光测定进一步证实了XLMC3R与XLmRAPS对等离子体膜的共定位和体外相互作用。我们的结果表明,XLMRAP2.L / S可以改善α-MSH刺激的XLMC3RS信号传导并抑制它们的表面表达。此外,XLMC3R.1在XLMRAP1.1的存在下显示了配体和表面表达上的类似型材。总之,XLMC3R.L和XLMC3R的不同药理调制由双MRAP2蛋白质阐明了Melanocortin系统在Tetrapod脊椎动物的基因组重复期间的功能一致性。

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