期刊
GENERAL AND COMPARATIVE ENDOCRINOLOGY
卷 328, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygcen.2022.114105
关键词
Endocrinology; Evolution; Stress; Mc2r; Mrap1; Chondrostean fish
资金
- Long Research Endowment at the University of Denver
- National Science Foundation Postdoctoral Fellowship [DBI-2109626]
This study examined the structure and pharmacological properties of Mc2r receptor in the Senegal bichir and found that it depends on Mrap1 and is selectively activated by ACTH. These findings suggest that these functional characteristics are ancestral to all bony fish Mc2rs.
In bony vertebrates, melanocortin 2 receptor (Mc2r) specifically binds adrenocorticotropic hormone (ACTH) and is responsible for mediating anterior pituitary signaling that stimulates corticosteroid production in the adrenal gland/interrenal cells. In bony fishes Mc2r requires the chaperoning of an accessory protein (Mrap1) to traffic to the membrane surface and bind ACTH. Here, we evaluated the structure and pharmacological properties of Mc2r from the Senegal bichir (Polypterus senegalus), which represents the most basal bony fish from which an Mc2r has been pharmacologically studied to date. In our experiments, cDNA constructs of the Mc2r from the Senegal bichir (sbMc2r) and various vertebrate Mrap1s were heterologously co-expressed in Chinese hamster ovary (CHO) cells, stimulated by ACTH or melanocyte-stimulating hormone (alpha-MSH) ligands, and assessed using a luciferase re-porter gene assay. When expressed without an Mrap1, sbMc2r was not activated by ACTH. When co-expressed with Mrap1 from either chicken (Gallus gallus) or bowfin (Amia calva), sbMc2r could be activated in a dose -dependent manner by ACTH, but not alpha-MSH. Co-expression of sbMrap2 with sbMc2r resulted in no detectable activation of the receptor. Collectively, these results demonstrate that sbMc2r has pharmacological properties similar to those of Mc2rs of later-evolved bony fishes, such as Mrap1 dependence and ACTH selectivity, indi-cating that these qualities of Mc2r function are ancestral to all bony fish Mc2rs.
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