Elephant Shark Melanocortin Receptors: Novel Interactions with MRAP1 and Implication for the HPI Axis

Authors

• Emily Barney, University of Denver
• Michael R. Dores, Hofstra University
• Danielle McAvoy, University of Denver
• Perry Davis, University of Denver
• Rona-Cristina Racareanu, Hofstra University
• Ayuko Iki, University of Tokyo
• Susumu Hyodo, University of Tokyo
• Robert Dores, University of DenverFollow

Publication Date

11-20-2018

Document Type

Article

Organizational Units

College of Natural Science and Mathematics, Biological Sciences

Keywords

Melanocortin receptors, MRAP1, MRAP2, Elephant shark, HPI

Abstract

The presence of Mrap1 and Mrap2 orthologs in the genome of the elephant shark (es), a cartilaginous fish, presented an opportunity to evaluate the potential interactions between these accessory proteins and melanocortin receptors of a cartilaginous fish. RT-PCR analysis indicated that Mrap1 mRNA was present in interrenal, brain, and pituitary tissue with mRNA for Mc2R, Mc3R, Mc4R, and Mc5r. Co-expression of esMrap1 cDNA with esMc2r cDNA or esMc5r cDNA in CHO cells increased sensitivity to stimulation with ACTH(1–24) 10 fold and 100 fold, respectfully, but had no effect on sensitivity to stimulation with DesAc-αMSH [i.e., ACTH(1–13)NH2] for either receptor, and had no effect on the ligand sensitivity of either esMc3r or esMc4r. Fluorescence image analysis indicated co-localization of esMrap1/esMc2r, and esMrap1/esMc5r on the plasma membrane; however, cell surface ELISA analysis indicated that co-expression with esMrap1 had no effect, positive or negative, on the trafficking of either esMc2r or esMc5r to the plasma membrane. RT-PCR analysis also indicated that Mrap2 mRNA, as well as, mRNAs for Mc2r, Mc3r, Mc4r, and Mc5r could be detected in brain tissue, however no Mrap2 mRNA was detected in interrenal tissue. Co-expression of esMrap2 in CHO cells with, respectively, esMc2r, esMc4r, or esMc5r had no effect on ligand sensitivity. However, co-expression of esMrap2 with esMc3r did lower sensitivity to stimulation by DesAc-αMSH 10 fold. These observations are discussed in the context of the parallel evolution of melanocortin receptors and their accessory proteins, and the hypothalamus/pituitary/adrenal axis and the hypothalamus/pituitary/interrenal axis in bony vertebrates and cartilaginous fishes.

Copyright Date

11-20-2018

Copyright Statement / License for Reuse

All Rights Reserved.

Rights Holder

Elsevier Inc.

Provenance

Received from author

Language

English (eng)

Extent

10 pgs

Publication Statement

Copyright is held by Elsevier Inc. User is responsible for all copyright compliance.

Publication Title

General and Comparative Endocrinology

Volume

272

Issue

C

First Page

42

Last Page

51

ISSN

1095-6840

Recommended Citation

Barney, E., Dores, M. R., McAvoy, D., Davis, P., Racareanu, R.-C., Iki, A., ..., & Dores, R. M. (2019). Elephant shark melanocortin receptors: Novel interactions with MRAP1 and implication for the HPI axis. General and Comparative Endocrinology, 272(C), 42–51. DOI: 10.1016/j.ygcen.2018.11.009

DOI Link

https://doi.org/10.1016/j.ygcen.2018.11.009