Regulation of Melanocortin-4 Receptor Pharmacology by Two Isoforms of Melanocortin Receptor Accessory Protein 2 in Topmouth Culter (Culter alburnus)
Regulation of Melanocortin-4 Receptor Pharmacology by Two Isoforms of Melanocortin Receptor Accessory Protein 2 in Topmouth Culter (Culter alburnus)
复制标题
黑皮质素受体辅助蛋白 2 的两种亚型对顶嘴鲌 (Culter alburnus) 中 Melanocortin-4 受体药理学的调节
DOI：
10.3389/fendo.2020.00538
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发表时间：
2020-08-14
影响因子：
5.2
通讯作者：
Tao, Ya-Xiong
中科院分区：
文献类型：
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作者：
Tao, Min;Ji, Ren-Lei;Tao, Ya-Xiong
黑色素皮质素-4受体（MC4R）在多种生理过程的调控中发挥着重要作用，MC4R与黑色素皮质素受体附属蛋白2（MRAP2）的相互作用被认为在脊椎动物的能量平衡中起着关键作用。顶口鲻（Culter alburnus）是中国重要的淡水经济鱼类。在此，我们克隆了cultermc4r、mrap2a和mrap2b。qRT-PCR显示，mc4r、mrap2a和mrap2b主要在中枢神经系统中表达。在外周，mc4randmrap2b在雄性中表达得更广泛，而mrap2aw在雌性中表达得更广泛。Culter MC4R能与四种多肽激动剂结合，并能剂量依赖性地增加细胞内cAMP的产生。Culter MC4R在cAMP和ERK1/2通路中都具有组成性活性，而cAMP和ERK1/2通路受Culter MRAP2a和MRAP2b的不同调控。Culter MRAP2a能显著增加B（max）并降低激动剂刺激的cAMP，而MRAP2b能增加细胞表面和总表达，但不影响B（max）和激动剂刺激的cAMP。这些结果将有助于研究 MC4R 可能参与顶口秆的潜在生理过程。
Melanocortin-4 receptor (MC4R) plays important roles in regulation of multiple physiological processes, and interaction of MC4R and melanocortin receptor accessory protein 2 (MRAP2) is suggested to play pivotal role in energy balance of vertebrates. Topmouth culter (Culter alburnus) is an economically important freshwater fish in China. Herein we cloned cultermc4r, mrap2a, andmrap2b. Cultermc4rconsisted of a 981 bp open reading frame encoding a protein of 326 amino acids. qRT-PCR revealed thatmc4r, mrap2a, andmrap2bwere primarily expressed in the central nervous system. In the periphery,mc4randmrap2bwere expressed more widely in the male, whilemrap2awas expressed more widely in the female. Culter MC4R could bind to four peptide agonists and increase intracellular cAMP production dose dependently. Culter MC4R was constitutively active in both cAMP and ERK1/2 pathways, which was differentially regulated by culter MRAP2a and MRAP2b. Culter MRAP2a significantly increased B(max)and decreased agonist-stimulated cAMP, while MRAP2b increased cell surface and total expression but did not affect B(max)and agonist-stimulated cAMP. These results will aid the investigation of the potential physiological processes that MC4R might be involved in topmouth culter.