ArticleThe Journal of biological chemistry2015
Adrenocorticotropic Hormone (ACTH) Responses Require Actions of the Melanocortin-2 Receptor Accessory Protein on the Extracellular Surface of the Plasma Membrane.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Adipocyte-specific MC2R overexpression exerts minimal metabolic effects in mice.Laboratory animal research · 2026Article
- Fecal microbiota transplantation mitigates cardiac remodeling and functional impairment in mice with chronic colitis.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Discovery of CRN04894: A Novel Potent Selective MC2R Antagonist.ACS medicinal chemistry letters · 2024Article
- Buckle up! How the nano-seatbelt MRAP1 fastens ACTH in its orthosteric seat.Cell research · 2023Article
- Structural basis of signaling regulation of the human melanocortin-2 receptor by MRAP1.Cell research · 2023Article
- Identification of MRAP protein family as broad-spectrum GPCR modulators.Clinical and translational medicine · 2022Article
- Article
- Regulation of Melanocortin-3 and -4 Receptors by Isoforms of Melanocortin-2 Receptor Accessory Protein 1 and 2.Biomolecules · 2022Article
- Pharmacokinetics of the Melanocortin Type 1 Receptor Agonist PL8177 After Subcutaneous Administration.Drugs in R&D · 2021Article
- Hypothesis and Theory: Evaluating the Co-Evolution of the Melanocortin-2 Receptor and the Accessory Protein MRAP1.Frontiers in endocrinology · 2021Article
- Membrane orientation and oligomerization of the melanocortin receptor accessory protein 2.The Journal of biological chemistry · 2020Article
- STARD1 Functions in Mitochondrial Cholesterol Metabolism and Nascent HDL Formation. Gene Expression and Molecular mRNA Imaging Show Novel Splicing and a 1:1 Mitochondrial Association.Frontiers in endocrinology · 2020Review
- Identifying Common Features in the Activation of Melanocortin-2 Receptors: Studies on theInternational journal of molecular sciences · 2019Article
- ACTH signalling and adrenal development: lessons from mouse models.Endocrine connections · 2019Review
- Transgenerational hypocortisolism and behavioral disruption are induced by the antidepressant fluoxetine in male zebrafishProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Regulation of Lipolytic Response and Energy Balance by Melanocortin 2 Receptor Accessory Protein (MRAP) in Adipocytes.Diabetes · 2018Article
- Neonatal presentation of familial glucocorticoid deficiency with a MRAP mutation: A case report.Molecular genetics and metabolism reports · 2016Article
- A novel role for pigment genes in the stress response in rainbow trout (Oncorhynchus mykiss).Scientific reports · 2016Article
- ACTH Antagonists.Frontiers in endocrinology · 2016Review
- Dual Topology of the Melanocortin-2 Receptor Accessory Protein Is Stable.Frontiers in endocrinology · 2016Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The melanocortin-2 (MC2) receptor is a G protein-coupled receptor that mediates responses to ACTH. The MC2 receptor acts in concert with the MC2 receptor accessory protein (MRAP) that is absolutely required for ACTH binding and signaling. MRAP has a single transmembrane domain and forms a highly unusual antiparallel homodimer that is stably associated with MC2 receptors at the plasma membrane. Despite the physiological importance of the interaction between the MC2 receptor and MRAP, there is little understanding of how the accessory protein works. The dual topology of MRAP has made it impossible to determine whether highly conserved and necessary regions of MRAP are required on the intracellular or extracellular face of the plasma membrane. The strategy used here was to fix the orientation of two antiparallel MRAP molecules and then introduce inactivating mutations on one side of the membrane or the other. This was achieved by engineering proteins containing tandem copies of MRAP fused to the amino terminus of the MC2 receptor. The data firmly establish that only the extracellular amino terminus (Nout) copy of MRAP, oriented with critical segments on the extracellular side of the membrane, is essential. The transmembrane domain of MRAP is also required in only the Nout orientation. Finally, activity of MRAP-MRAP-MC2-receptor fusion proteins with inactivating mutations in either MRAP or the receptor was rescued by co-expression of free wild-type MRAP or free wild-type receptor. These results show that the basic MRAP-MRAP-receptor signaling unit forms higher order complexes and that these multimers signal.
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