Previous studies on bony vertebrate MC2R orthologs (i.e., ray finned fishes, amphibians, reptiles, birds,
and mammals) have shown that these MC2R orthologs have an obligatory requirement for interaction
with bony vertebrate MRAP1 orthologs to a) allow for the trafficking of the MC2R ortholog to the plasma
membrane; and b) to allow activation by ACTH, but not by any MSH-sized ligand. In addition, previous
studies have found that co-expression of teleost and mammalian MC4R orthologs with corresponding
MRAP2 has positive effects on sensitivity to stimulation by aMSH or ACTH. MRAP1 and MRAP2 paralogs
have been detected in the genome of a cartilaginous fish (elephant shark), yet two cartilaginous fish
MC2R or... More
Previous studies on bony vertebrate MC2R orthologs (i.e., ray finned fishes, amphibians, reptiles, birds,
and mammals) have shown that these MC2R orthologs have an obligatory requirement for interaction
with bony vertebrate MRAP1 orthologs to a) allow for the trafficking of the MC2R ortholog to the plasma
membrane; and b) to allow activation by ACTH, but not by any MSH-sized ligand. In addition, previous
studies have found that co-expression of teleost and mammalian MC4R orthologs with corresponding
MRAP2 has positive effects on sensitivity to stimulation by aMSH or ACTH. MRAP1 and MRAP2 paralogs
have been detected in the genome of a cartilaginous fish (elephant shark), yet two cartilaginous fish
MC2R orthologs (elephant shark and red stingray) do not apparently require MRAP1 for trafficking to
the plasma membrane when expressed in Chinese Hamster Ovary (CHO) cells, and both orthologs can
be activated by either ACTH or MSH-sized ligands. This study was done to determine whether sensitivity
to stimulation by ACTH(1-24) or Des-Acetyl-aMSH is affected when stingray (sr) MC1R, MC2R, MC3R,
MC4R or MC5R were co-expressed in CHO cells with either elephant shark (es) MRAP1 or esMRAP2.
The results indicated that co-expression with heterologous MRAP1 increased the sensitivity of all five
stingray melanocortin receptors for srACTH(1-24), but had not statistically significant effect on stimulation by srDes-Acetyl-aMSH for any of the stingray melanocortin receptors. Conversely, co-expression
with esMRAP2 only enhanced sensitivity for srDes-Acetyl-aMSH for srMC4R, but had no effect on the
other stingray orthologs, and there was no increase in sensitivity for srACTH(1-24) for any of the stingray
melanocortin receptors. It appears then that some stingray melanocortin receptors have retained the
ability to interact with a cartilaginous MRAP1 paralog. These results are discussed with reference to radiation of MRAP-related accessory proteins in cartilaginous fishes.
