Pharmacological modulation of two melanocortin-5 receptors by MRAP2 proteins in zebrafish.

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Abstract

Melanocortin receptor accessory protein 2 (MRAP2) plays an important role in regulating melanocortin receptors. In zebrafish, MRAP2a and MRAP2b show distinct pharmacological effects on MC4R activity, but how MRAP2 protein regulates other zebrafish melanocortin receptors is barely studied. Zebrafish have two mc5r genes: mc5ra and mc5rb, it is still vague which one is the homologous isoform to the mammalian paralog. Here we utilize synteny and phylogenetic analysis to demonstrate the evolutionary conservation of zebrafish MC5Ra and MC5Rb among different species. We also show that MRAP2a and MRAP2b could interact and regulate surface expression of two MC5R receptors. Bimolecular fluorescence complementation (BiFC) studies suggest that zebrafish MC5Rs could form homo- and hetero- dimers, which are suppressed by co-expression with MRAP2 proteins. In comparison with mammalian MC5R-MRAP2 system and different pharmacological effects of zMRAP2 protein on MC5Rs, zmc5ra is identified as the evolutionary homologous paralog to the mammals and it is regulated by metabolic state in zebrafish brain region.

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Journal

Journal ID (iso-abbrev): J Mol Endocrinol

Title: Journal of molecular endocrinology

Publisher: Bioscientifica

ISSN (Electronic): 1479-6813

ISSN (Print): 0952-5041

Publication date (Electronic): Oct 01 2018

Affiliations

[1 ] M Zhu, Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.

[2 ] M Wang, Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.

[3 ] Y Chen, Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.

[4 ] C Zhang, Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.

Article

Publisher Item ID: JME-18-0104.R2

DOI: 10.1530/JME-18-0104

PubMed ID: 30400043

SO-VID: 741f8613-e84b-407c-8de9-7b6230ff84dc

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