Pharmacological modulation of the cAMP signaling of two isoforms of melanocortin-3 receptor by melanocortin receptor accessory proteins in the tetrapod Xenopus laevis
| Autor: | Xiao-Mei Yang, Cong Zhang, Zhe Kuang, Liumei Lu, Yue Zhai, Chao Zhang, Bopei Jiang, Li-Na Jin, Ying Xu, Meng Wang, Jihong Zheng, Gufa Lin, Lei Li |
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| Rok vydání: | 2021 |
| Předmět: |
Gene isoform
biology business.industry Endocrinology Diabetes and Metabolism Research Xenopus MRAPs MC3R Sequence alignment tetrapod RC648-665 biology.organism_classification Diseases of the endocrine glands. Clinical endocrinology Melanocortin 3 receptor Cell biology Xenopus laevis Endocrinology Melanocortin receptor Internal Medicine Medicine xenopus laevism Melanocortin business Receptor Synteny |
| Zdroj: | Endocrine Connections Endocrine Connections, Vol 10, Iss 11, Pp 1477-1488 (2021) |
| ISSN: | 2049-3614 |
| Popis: | 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 pharmacological effect could be directly influenced by the presence of melanocortin receptor 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. |
| Databáze: | OpenAIRE |
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