University of Denver, Department of Biological Sciences, Denver, CO, USA.
University of Denver, Department of Biological Sciences, Denver, CO, USA.
Gen Comp Endocrinol. 2020 Aug 1;294:113476. doi: 10.1016/j.ygcen.2020.113476. Epub 2020 Mar 31.
The melanocortin-2 receptor (MC2R) and the melanocortin-5 receptor (MC5R) are found on the same chromosome in most vertebrate genomes, and for the species analyzed in this study, MC2R and MC5R are co-expressed in glucocorticoid-producing cells that also express the accessory protein MRAP1. Since MRAP1 affects the ligand sensitivity of MC2R orthologs, this study tested the hypothesis that co-expression of MC5R with MRAP1 would also affect the ligand sensitivity of MC5R. The hypothesis was confirmed for stingray, rainbow trout, and chicken, MC5R orthologs. However, elephant shark MC5R was not affected in the same way by co-expression of MRAP1. It appears that, for some MC5R orthologs (i.e., stingray, rainbow trout, and chicken), a docking site for the R/KKRRP motif of ACTH(1-24) may become exposed on the receptor following co-expression with MRAP1. However, for elephant shark MC5R co-expression with MRAP1 may not affect engagement ACTH(1-24). Hence during the radiation of the chordates, the interaction between MRAP1 and MC5R has diverged.
黑皮质素-2 受体 (MC2R) 和黑皮质素-5 受体 (MC5R) 在大多数脊椎动物基因组中位于同一条染色体上，在本研究分析的物种中，MC2R 和 MC5R 共同表达在产生糖皮质激素的细胞中，这些细胞也表达辅助蛋白 MRAP1。由于 MRAP1 影响 MC2R 同源物的配体敏感性，因此本研究检验了这样一个假设，即 MC5R 与 MRAP1 的共表达也会影响 MC5R 的配体敏感性。该假设在黄貂鱼、虹鳟鱼和鸡的 MC5R 同源物中得到了证实。然而，象鲨的 MC5R 并没有受到 MRAP1 共表达的相同影响。似乎对于一些 MC5R 同源物（即黄貂鱼、虹鳟鱼和鸡），MRAP1 共表达后，ACTH(1-24)的 R/KKRRP 基序的对接位点可能会暴露在受体上。然而，对于象鲨 MC5R，MRAP1 共表达可能不会影响 ACTH(1-24)的结合。因此，在脊索动物的辐射过程中，MRAP1 和 MC5R 之间的相互作用已经发生了分歧。
