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

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-PC...

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Autores principales:	Ren-Lei Ji, Lu Huang, Yin Wang, Ting Liu, Si-Yu Fan, Min Tao, Ya-Xiong Tao
Formato:	article
Lenguaje:	EN
Publicado:	Bioscientifica 2021
Materias:	melanocortin-3 receptor constitutive activity melanocortin-2 receptor accessory protein 2 signaling topmouth culter Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doi.org/10.1530/EC-21-0459 https://doaj.org/article/868a0c96feeb4ca99f659cc9f89207f0
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spelling	oai:doaj.org-article:868a0c96feeb4ca99f659cc9f89207f02021-11-18T07:16:24ZTopmouth culter melanocortin-3 receptor: regulation by two isoforms of melanocortin-2 receptor accessory protein 2https://doi.org/10.1530/EC-21-04592049-3614https://doaj.org/article/868a0c96feeb4ca99f659cc9f89207f02021-11-01T00:00:00Zhttps://ec.bioscientifica.com/view/journals/ec/10/11/EC-21-0459.xmlhttps://doaj.org/toc/2049-3614Melanocortin-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 RIA, and caMC3R expression was quantified with flow cytometry. We showed that cul ter mc3r had higher expression in the CNS. All agonists could bind and stimulate caMC3R to increase dose dependently intracellular cAMP accumulation. Compared to human MC3R, culter MC3R showed higher constitutive activity, higher efficacies, and Rmax to alpha-melanocyte-stimulating hormone (α-MSH), des-α-MSH, and adrenocorticotrophic hormone. 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 MRAP2b had different effects on expression and signaling of caMC3R. In addit ion, expression analysis suggested that MRAP2s, receptors, and hormones might play differ ent roles in regulating culter development and growth.Ren-Lei JiLu HuangYin WangTing LiuSi-Yu FanMin TaoYa-Xiong TaoBioscientificaarticlemelanocortin-3 receptorconstitutive activitymelanocortin-2 receptor accessory protein 2signalingtopmouth culterDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENEndocrine Connections, Vol 10, Iss 11, Pp 1489-1501 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	melanocortin-3 receptor constitutive activity melanocortin-2 receptor accessory protein 2 signaling topmouth culter Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	melanocortin-3 receptor constitutive activity melanocortin-2 receptor accessory protein 2 signaling topmouth culter Diseases of the endocrine glands. Clinical endocrinology RC648-665 Ren-Lei Ji Lu Huang Yin Wang Ting Liu Si-Yu Fan Min Tao Ya-Xiong Tao Topmouth culter melanocortin-3 receptor: regulation by two isoforms of melanocortin-2 receptor accessory protein 2
description	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 RIA, and caMC3R expression was quantified with flow cytometry. We showed that cul ter mc3r had higher expression in the CNS. All agonists could bind and stimulate caMC3R to increase dose dependently intracellular cAMP accumulation. Compared to human MC3R, culter MC3R showed higher constitutive activity, higher efficacies, and Rmax to alpha-melanocyte-stimulating hormone (α-MSH), des-α-MSH, and adrenocorticotrophic hormone. 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 MRAP2b had different effects on expression and signaling of caMC3R. In addit ion, expression analysis suggested that MRAP2s, receptors, and hormones might play differ ent roles in regulating culter development and growth.
format	article
author	Ren-Lei Ji Lu Huang Yin Wang Ting Liu Si-Yu Fan Min Tao Ya-Xiong Tao
author_facet	Ren-Lei Ji Lu Huang Yin Wang Ting Liu Si-Yu Fan Min Tao Ya-Xiong Tao
author_sort	Ren-Lei Ji
title	Topmouth culter melanocortin-3 receptor: regulation by two isoforms of melanocortin-2 receptor accessory protein 2
title_short	Topmouth culter melanocortin-3 receptor: regulation by two isoforms of melanocortin-2 receptor accessory protein 2
title_full	Topmouth culter melanocortin-3 receptor: regulation by two isoforms of melanocortin-2 receptor accessory protein 2
title_fullStr	Topmouth culter melanocortin-3 receptor: regulation by two isoforms of melanocortin-2 receptor accessory protein 2
title_full_unstemmed	Topmouth culter melanocortin-3 receptor: regulation by two isoforms of melanocortin-2 receptor accessory protein 2
title_sort	topmouth culter melanocortin-3 receptor: regulation by two isoforms of melanocortin-2 receptor accessory protein 2
publisher	Bioscientifica
publishDate	2021
url	https://doi.org/10.1530/EC-21-0459 https://doaj.org/article/868a0c96feeb4ca99f659cc9f89207f0
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Topmouth culter melanocortin-3 receptor: regulation by two isoforms of melanocortin-2 receptor accessory protein 2

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