Regulation of melanocortin-1 receptor pharmacology by melanocortin receptor accessory protein 2 in orange-spotted grouper (Epinephelus coioides)

Ji, Liqin; Rao, Ying-Zhu; Zhang, Yong; Chen, Rong; Tao, Ya‐Xiong

doi:10.1016/j.ygcen.2019.113291

Cited by 9 publications

(7 citation statements)

References 67 publications

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“…Only three studies have investigated the pharmacological properties of fish MC3Rs so far ( 43 , 44 , 49 ). Of interest, two studies reported high constitutive activities in zebrafish and channel catfish MC3Rs ( 43 , 49 ), similar to the results in teleost MC4Rs ( 39 , 40 , 41 , 47 , 50 , 51 , 52 , 53 ) and MC1R ( 54 ). In this study, topmouth culter ( Culteralburnus ) was used as an animal model to explore the physiology and pharmacology of culter MC3R.…”

Section: Introductionsupporting

confidence: 69%

Topmouth culter melanocortin-3 receptor: regulation by two isoforms of melanocortin-2 receptor accessory protein 2

Huang

Wang

et al. 2021

Endocrine Connections

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Melanocortin-3 receptor (MC3R) is a regulator of energy homeostasis, and interaction of MC3R and melanocortin-2 receptor accessory protein 2 (MRAP2) plays a critical role in MC3R signaling of mammals. However, the physiological roles of MC3R in teleosts are not well understood. In this study, qRT-PCR was used to measure gene expression. Radioligand binding assay was used to study the binding properties of topmouth culter MC3R (caMC3R). Intracellular cAMP generation was determined by radioimmunoassay and caMC3R expression was quantified with flow cytometry. We showed that culter mc3r had higher expression in the central nervous system. All agonists could bind and stimulate caMC3R to increase dose-dependently intracellular cAMP accumulation. Compared to hMC3R, culter MC3R showed higher constitutive activity, higher efficacies and Rmax to α-MSH, des-α-MSH, and ACTH. Both caMRAP2a and caMRAP2b markedly decreased caMC3R basal cAMP production. However, only caMRAP2a significantly decreased cell surface expression, Bmax and Rmax of caMC3R. Expression analysis suggested that MRAP2a and MRAP2b might be more important in regulating MC3R/MC4R signaling during larval period, and reduced mc3r, mc4r, and pomc expression might be primarily involved in modulation of MC3R/MC4R in adults. These data indicated that the cloned caMC3R was a functional receptor. MRAP2a and MRAP2a had different effects on expression and signaling of caMC3R. In addition, expression analysis suggested that MRAP2s, receptors, and hormone might play different roles in regulating culter development and growth.

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Section: Introductionsupporting

confidence: 69%

Topmouth culter melanocortin-3 receptor: regulation by two isoforms of melanocortin-2 receptor accessory protein 2

Huang

Wang

et al. 2021

Endocrine Connections

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“…In humans, MC1R protein was localized in Leydig and corpus luteum cells [ 24 ], the functions of which are related to the synthesis of steroids in males and females, respectively. In fish, mc1r transcripts are detected in adult organs, including the testes and ovaries, whereas in zebrafish, they were solely detected in the testes [ 2 , 25 , 26 ]. It was also shown that mc2r is expressed in both female and male gonads as previously reported in zebrafish [ 3 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

Role of the Melanocortin System in Gonadal Steroidogenesis of Zebrafish

Navarro

Crespo

Schulz

et al. 2022

Animals

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In teleost, as in other vertebrates, stress affects reproduction. A key component of the stress response is the pituitary secretion of the adrenocorticotropic hormone (ACTH), which binds to the melanocortin 2 receptor (MC2R) in the adrenal glands and activates cortisol biosynthesis. In zebrafish, Mc2r was identified in male and female gonads, while ACTH has been shown to have a physiological role in modulating reproductive activity. In this study, the hypothesis that other melanocortins may also affect how the zebrafish gonadal function is explored, specifically steroid biosynthesis, given the presence of members of the melanocortin signaling system in zebrafish gonads. Using cell culture, expression analysis, and cellular localization of gene expression, our new observations demonstrated that melanocortin receptors, accessory proteins, antagonists, and agonists are expressed in both the ovary and testis of zebrafish (n = 4 each sex). Moreover, melanocortin peptides modulate both basal and gonadotropin-stimulated steroid release from zebrafish gonads (n = 15 for males and n = 50 for females). In situ hybridization in ovaries (n = 3) of zebrafish showed mc1r and mc4r in follicular cells and adjacent to cortical alveoli in the ooplasm of previtellogenic and vitellogenic oocytes. In zebrafish testes (n = 3), mc4r and mc1r were detected exclusively in germ cells, specifically in spermatogonia and spermatocytes. Our results suggest that melanocortins are, directly or indirectly, involved in the endocrine control of vitellogenesis in females, through modulation of estradiol synthesis via autocrine or paracrine actions in zebrafish ovaries. Adult zebrafish testes were sensitive to low doses of ACTH, eliciting testosterone production, which indicates a potential role of this peptide as a paracrine regulator of testicular function.

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“…In lower vertebrates, especially the teleosts, Mc1r mainly participates in the dermal melanin synthesis and melanophore dispersion ( 21 , 22 ). Interestingly, the rainbow trout mc1r transcript is strongly associated with the stress response ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

“…In the zebrafish, pineal AgRP2 neurons projected to the lateral tubular nucleus, specifically antagonized zMc1r signaling and stimulated the hypothalamic synthesis of two melanin concentrating hormones (MCH and MCH-like) ( 21 ). Moreover, chordate Mc1r signaling is regulated by Mrap proteins in red stingray (Dasyatis akajei) ( 22 ) and orange-spotted grouper (Epinephelus coioides) ( 23 ) and is strongly associated with the stress response in the rainbow trout (Oncorhynchus mykiss) ( 24 ) and zebrafish (Danio rerio) ( 25 ).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Modulation of Melanocortin 1 Receptor Signaling by Mrap Proteins in Xenopus tropicalis

Tai

Zhang²,

Yao

et al. 2022

Front. Endocrinol.

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The melanocortin system consists of five G protein–coupled receptors (MC1R-MC5R), the bidirectional endogenous ligands (MSH and Agouti families), and accessory proteins (MRAP1 and MRAP2). Accumulative studies of vertebrate species find high expression level of melanocortin 1 receptor (MC1R) in the dermal melanocyte and elucidate the essential roles in the skin and fur pigmentation, morphological background adaptation, and stress response. The diploid amphibian Xenopus tropicalis (xt) has been utilized as a fantastic animal model for embryonic development and studies of physiological cryptic colouring and environmental adaptiveness. However, the interaction of xtMc1r signaling with xtMrap proteins has not been assessed yet. In this study, we carried out in silico evolutionary analysis of protein alignment and genetic phylogenetic and genomic synteny of mc1r among various vertebrates. Ubiquitous expression of mrap1 and mrap2 and the co-expression with mc1r transcripts in the skin were clearly observed. Co-immunoprecipitation (ip) and fluorescent complementary approach validated the direct functional interaction of xtMc1r with xtMrap1 or xtMrap2 proteins on the plasma membrane. Pharmacological assay showed the improvement of the constitutive activity and alpha melanocyte-stimulating hormone (α-MSH) stimulated plateau without dramatic alteration of the cell surface translocation of xtMc1r in the presence of xtMrap proteins. Overall, the pharmacological modulation of xtMc1r by dual xtMrap2 proteins elucidated the potential role of this protein complex in the regulation of proper dermal function in amphibian species.

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Regulation of melanocortin-1 receptor pharmacology by melanocortin receptor accessory protein 2 in orange-spotted grouper (Epinephelus coioides)

Cited by 9 publications

References 67 publications

Topmouth culter melanocortin-3 receptor: regulation by two isoforms of melanocortin-2 receptor accessory protein 2

Topmouth culter melanocortin-3 receptor: regulation by two isoforms of melanocortin-2 receptor accessory protein 2

Role of the Melanocortin System in Gonadal Steroidogenesis of Zebrafish

Pharmacological Modulation of Melanocortin 1 Receptor Signaling by Mrap Proteins in Xenopus tropicalis

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