ArticleThe Journal of biological chemistry2009
Opposite effects of the melanocortin-2 (MC2) receptor accessory protein MRAP on MC2 and MC5 receptor dimerization and trafficking.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- MRAP2 modifies the signaling and oligomerization state of the melanocortin-4 receptor.Nature communications · 2025Article
- Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins.Pharmacological reviews · 2023Review
- Melanocortin-5 Receptor: Pharmacology and Its Regulation of Energy Metabolism.International journal of molecular sciences · 2022Review
- Reversion of MRAP2 Protein Sequence Generates a Functional Novel Pharmacological Modulator for MC4R Signaling.Biology · 2022Article
- Selective Interactions of Mouse Melanocortin Receptor Accessory Proteins with Somatostatin Receptors.Cells · 2022Article
- Characterization of the chicken melanocortin 5 receptor and its potential role in regulating hepatic glucolipid metabolism.Frontiers in physiology · 2022Article
- Review
- Regulation of Melanocortin-4 Receptor Pharmacology by Two Isoforms of Melanocortin Receptor Accessory Protein 2 in Topmouth Culter (Frontiers in endocrinology · 2020Article
- Analyzing the signaling properties of gar (Lepisosteus oculatus) melanocortin receptors: Evaluating interactions with MRAP1 and MRAP2.General and comparative endocrinology · 2019Article
- Pharmacological modulation of MRAP2 protein on melanocortin receptors in the sea lamprey.Endocrine connections · 2019Article
- Stability and Turnover of the ACTH Receptor Complex.Frontiers in endocrinology · 2019Review
- Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- A Direct in Vivo Comparison of the Melanocortin Monovalent Agonist Ac-His-DPhe-Arg-Trp-NHACS chemical neuroscience · 2017Article
- Loss of Mrap2 is associated with Sim1 deficiency and increased circulating cholesterol.The Journal of endocrinology · 2016Article
- An in Vitro and in Vivo Investigation of Bivalent Ligands That Display Preferential Binding and Functional Activity for Different Melanocortin Receptor Homodimers.Journal of medicinal chemistry · 2016Article
- Article
- Hypothesis and Theory: Revisiting Views on the Co-evolution of the Melanocortin Receptors and the Accessory Proteins, MRAP1 and MRAP2.Frontiers in endocrinology · 2016Article
- Dual Topology of the Melanocortin-2 Receptor Accessory Protein Is Stable.Frontiers in endocrinology · 2016Article
- Adrenocorticotropic Hormone (ACTH) Responses Require Actions of the Melanocortin-2 Receptor Accessory Protein on the Extracellular Surface of the Plasma Membrane.The Journal of biological chemistry · 2015Article
- Intracellular signaling mechanisms of the melanocortin receptors: current state of the art.Cellular and molecular life sciences : CMLS · 2015Review
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Authors and funding
2 authors.
Funding
Abstract
MC2 (ACTH) receptors require MC2 receptor accessory protein (MRAP) to reach the cell surface. In this study, we show that MRAP has the opposite effect on the closely related MC5 receptor. In enzyme-linked immunosorbent assay and microscopy experiments, MC2 receptor was retained in the endoplasmic reticulum in the absence of MRAP and targeted to the plasma membrane with MRAP. MC5 receptor was at the plasma membrane in the absence of MRAP, but trapped intracellularly when expressed with MRAP. Using bimolecular fluorescence complementation, where one fragment of yellow fluorescent protein (YFP) was fused to receptors and another to MRAP, we showed that MC2 receptor-MRAP dimers were present at the plasma membrane, whereas MC5 receptor-MRAP dimers were intracellular. Both MC2 and MC5 receptors co-precipitated with MRAP. MRAP did not alter expression of beta2-adrenergic receptors or co-precipitate with them. To determine if MRAP affects formation of receptor oligomers, we co-expressed MC2 receptors fused to YFP fragments in the presence or absence of MRAP. YFP fluorescence, reporting MC2 receptor homodimers, was readily detectable with or without MRAP. In contrast, MC5 receptor homodimers were visible in the absence of MRAP, but little fluorescence was observed by microscopic analysis when MRAP was co-expressed. Co-precipitation of differentially tagged receptors confirmed that MRAP blocks MC5 receptor dimerization. The regions of MRAP required for its effects on MC2 and MC5 receptors differed. These results establish that MRAP forms stable complexes with two different melanocortin receptors, facilitating surface expression of MC2 receptor but disrupting dimerization and surface localization of MC5 receptor.
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