Dores Robert M, Garcia Yesenia
Department of Biological Sciences, University of Denver, Denver, CO 80210, USA.
Department of Biological Sciences, University of Denver, Denver, CO 80210, USA.
Mol Cell Endocrinol. 2015 Jun 15;408:12-22. doi: 10.1016/j.mce.2014.12.022. Epub 2015 Jan 5.
A critical regulatory component of the hypothalamus/pituitary/adrenal axis (HPA) in mammals, reptiles and birds, and in the hypothalamus/pituitary/interrenal (HPI) axis of amphibians and teleosts (modern bony fishes) is the strict ligand selectivity of the melanocortin-2 receptor (MC2R). Tetrapod and teleost MC2R orthologs can only be activated by the anterior pituitary hormone, ACTH, but not by any of the MSH-sized ligands coded in POMC. In addition, both tetrapod and teleost MC2R orthologs require co-expression with the accessory protein, MRAP. However, the MC2R ortholog of the elephant shark, a cartilaginous fish, can be activated by either ACTH or the MSH-sized ligands, and the elephant shark MC2R ortholog does not require co-expression with an MRAP for activation. Given these observations, this review will provide a scenario for the co-evolution of MC2R and MRAP, based on the assumption that the obligate interaction between MC2R and MRAP evolved during the early radiation of the ancestral bony fishes.
在哺乳动物、爬行动物和鸟类的下丘脑/垂体/肾上腺轴（HPA）以及两栖动物和硬骨鱼（现代硬骨鱼类）的下丘脑/垂体/肾间组织（HPI）轴中，一个关键的调节成分是黑皮质素-2受体（MC2R）严格的配体选择性。四足动物和硬骨鱼的MC2R直系同源物只能被垂体前叶激素促肾上腺皮质激素（ACTH）激活，而不能被阿片-促黑素细胞皮质素原（POMC）编码的任何一种促黑素（MSH）大小的配体激活。此外，四足动物和硬骨鱼的MC2R直系同源物都需要与辅助蛋白MRAP共同表达。然而，软骨鱼姥鲨的MC2R直系同源物既可以被ACTH激活，也可以被MSH大小的配体激活，并且姥鲨的MC2R直系同源物激活时不需要与MRAP共同表达。基于这些观察结果，本综述将基于MC2R和MRAP之间的专一性相互作用是在原始硬骨鱼早期辐射过程中进化而来的这一假设，提供一个MC2R和MRAP共同进化的设想。
