Pharmacological modulation of the cAMP signaling of two isoforms of melanocortin-3 receptor by melanocortin receptor accessory proteins in the tetrapod Xenopus laevis

As a member of the seven-transmembrane rhodopsin-like G protein-coupled receptor superfamily, the melanocortin-3 receptor (MC3R) is vital for the regulation of energy homeostasis and rhythms synchronizing in mammals, and its pharm acological effect could be directly influenced by the presence of mel...

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Autores principales:	Ying Xu, Lei Li, Jihong Zheng, Meng Wang, Bopei Jiang, Yue Zhai, Liumei Lu, Cong Zhang, Zhe Kuang, Xiaomei Yang, Li-Na Jin, Gufa Lin, Chao Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Bioscientifica 2021
Materias:	xenopus laevism mraps mc3r tetrapod Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doi.org/10.1530/EC-21-0179 https://doaj.org/article/205b55b7cb1d4c4fb7736205567329e8
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spelling	oai:doaj.org-article:205b55b7cb1d4c4fb7736205567329e82021-11-18T07:12:30ZPharmacological modulation of the cAMP signaling of two isoforms of melanocortin-3 receptor by melanocortin receptor accessory proteins in the tetrapod Xenopus laevishttps://doi.org/10.1530/EC-21-01792049-3614https://doaj.org/article/205b55b7cb1d4c4fb7736205567329e82021-11-01T00:00:00Zhttps://ec.bioscientifica.com/view/journals/ec/10/11/EC-21-0179.xmlhttps://doaj.org/toc/2049-3614As a member of the seven-transmembrane rhodopsin-like G protein-coupled receptor superfamily, the melanocortin-3 receptor (MC3R) is vital for the regulation of energy homeostasis and rhythms synchronizing in mammals, and its pharm acological effect could be directly influenced by the presence of melanocortin rec eptor accessory proteins (MRAPs), MRAP1 and MRAP2. The tetrapod amphibian Xenopus laevis (xl) retains higher duplicated genome than extant teleosts and serves as an ideal model system for embryonic development and physiological studies. However, the melanocortin system of the Xenopus laevis has not yet been thoroughly evaluated. In this work, we performed sequence alignment, phylogenetic tree, and synteny analysis of two xlMC3Rs. Co-immunoprecipitation and immunofluorescence assay further confirmed the co-localization and in vitro interaction of xlMC3Rs with xlMRAPs on the plasma membrane. Our results demonstrated that xlMRAP2.L/S could improve α-MSH-stimulated xlMC3Rs signaling and suppress their surface expression. Moreover, xlMC3R.L showed a similar profile on the ligands and surface expression in the presence of xlMRAP1.L. Overall, the distinct pharmacological modulation of xlMC3R.L and xlMC3R.S by dual MRAP2 proteins elucidated the functional consistency of melanocortin system during genomic duplication of tetrapod vertebrates.Ying XuLei LiJihong ZhengMeng WangBopei JiangYue ZhaiLiumei LuCong ZhangZhe KuangXiaomei YangLi-Na JinGufa LinChao ZhangBioscientificaarticlexenopus laevismmrapsmc3rtetrapodDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENEndocrine Connections, Vol 10, Iss 11, Pp 1477-1488 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	xenopus laevism mraps mc3r tetrapod Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	xenopus laevism mraps mc3r tetrapod Diseases of the endocrine glands. Clinical endocrinology RC648-665 Ying Xu Lei Li Jihong Zheng Meng Wang Bopei Jiang Yue Zhai Liumei Lu Cong Zhang Zhe Kuang Xiaomei Yang Li-Na Jin Gufa Lin Chao Zhang Pharmacological modulation of the cAMP signaling of two isoforms of melanocortin-3 receptor by melanocortin receptor accessory proteins in the tetrapod Xenopus laevis
description	As a member of the seven-transmembrane rhodopsin-like G protein-coupled receptor superfamily, the melanocortin-3 receptor (MC3R) is vital for the regulation of energy homeostasis and rhythms synchronizing in mammals, and its pharm acological effect could be directly influenced by the presence of melanocortin rec eptor accessory proteins (MRAPs), MRAP1 and MRAP2. The tetrapod amphibian Xenopus laevis (xl) retains higher duplicated genome than extant teleosts and serves as an ideal model system for embryonic development and physiological studies. However, the melanocortin system of the Xenopus laevis has not yet been thoroughly evaluated. In this work, we performed sequence alignment, phylogenetic tree, and synteny analysis of two xlMC3Rs. Co-immunoprecipitation and immunofluorescence assay further confirmed the co-localization and in vitro interaction of xlMC3Rs with xlMRAPs on the plasma membrane. Our results demonstrated that xlMRAP2.L/S could improve α-MSH-stimulated xlMC3Rs signaling and suppress their surface expression. Moreover, xlMC3R.L showed a similar profile on the ligands and surface expression in the presence of xlMRAP1.L. Overall, the distinct pharmacological modulation of xlMC3R.L and xlMC3R.S by dual MRAP2 proteins elucidated the functional consistency of melanocortin system during genomic duplication of tetrapod vertebrates.
format	article
author	Ying Xu Lei Li Jihong Zheng Meng Wang Bopei Jiang Yue Zhai Liumei Lu Cong Zhang Zhe Kuang Xiaomei Yang Li-Na Jin Gufa Lin Chao Zhang
author_facet	Ying Xu Lei Li Jihong Zheng Meng Wang Bopei Jiang Yue Zhai Liumei Lu Cong Zhang Zhe Kuang Xiaomei Yang Li-Na Jin Gufa Lin Chao Zhang
author_sort	Ying Xu
title	Pharmacological modulation of the cAMP signaling of two isoforms of melanocortin-3 receptor by melanocortin receptor accessory proteins in the tetrapod Xenopus laevis
title_short	Pharmacological modulation of the cAMP signaling of two isoforms of melanocortin-3 receptor by melanocortin receptor accessory proteins in the tetrapod Xenopus laevis
title_full	Pharmacological modulation of the cAMP signaling of two isoforms of melanocortin-3 receptor by melanocortin receptor accessory proteins in the tetrapod Xenopus laevis
title_fullStr	Pharmacological modulation of the cAMP signaling of two isoforms of melanocortin-3 receptor by melanocortin receptor accessory proteins in the tetrapod Xenopus laevis
title_full_unstemmed	Pharmacological modulation of the cAMP signaling of two isoforms of melanocortin-3 receptor by melanocortin receptor accessory proteins in the tetrapod Xenopus laevis
title_sort	pharmacological modulation of the camp signaling of two isoforms of melanocortin-3 receptor by melanocortin receptor accessory proteins in the tetrapod xenopus laevis
publisher	Bioscientifica
publishDate	2021
url	https://doi.org/10.1530/EC-21-0179 https://doaj.org/article/205b55b7cb1d4c4fb7736205567329e8
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Pharmacological modulation of the cAMP signaling of two isoforms of melanocortin-3 receptor by melanocortin receptor accessory proteins in the tetrapod Xenopus laevis

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