ArticleClinical and translational medicine2022
Identification of MRAP protein family as broad-spectrum GPCR modulators.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Association of Mutations in theInternational journal of molecular sciences · 2026Pooled it
- GPCRs in CAR-T Cell Immunotherapy: Expanding the Target Landscape and Enhancing Therapeutic Efficacy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Cellular signatures of melanocortin pathway genes across the locus coeruleus.Acta neuropathologica communications · 2026Article
- Molecular insight into transcriptome profiling of aerobic exercise induced changes in aged skeletal muscle.npj aging · 2026Article
- Constitutive activity among orphan G protein-coupled receptors: Molecular mechanisms and pharmacological perspectives.Molecular pharmacology · 2026Review
- The accessory protein MRAP2 directly interacts with melanocortin-3 receptor to enhance signaling.Science signaling · 2025Article
- MRAP2 modifies the signaling and oligomerization state of the melanocortin-4 receptor.Nature communications · 2025Article
- Canine genome-wide association study identifiesScience (New York, N.Y.) · 2025Article
- Obesity-associated MRAP2 variants impair multiple MC4R-mediated signaling pathways.Human molecular genetics · 2025Article
- Intracellular GPCR modulators enable precision pharmacology.npj drug discovery · 2025Review
- Pharmacological modulation of MRAP2 protein on murine melatonin receptor signaling.Frontiers in endocrinology · 2025Article
- MRAP2a Binds and Modulates Activity and Localisation of Prokineticin Receptor 1 in Zebrafish.International journal of molecular sciences · 2024Article
- Single transmembrane GPCR modulating proteins: neither single nor simple.Protein & cell · 2024Article
- MRAP2 Inhibits β-Arrestin-2 Recruitment to the Prokineticin Receptor 2.Current issues in molecular biology · 2024Article
- Genes Selectively Expressed in Rat Organs.Current genomics · 2024Article
- Is the Neuropeptide PEN a Ligand of GPR83?International journal of molecular sciences · 2023Article
- Identification of MRAP protein family as broad-spectrum GPCR modulators.Clinical and translational medicine · 2022Article
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe melanocortin receptor accessory proteins (MRAP1 and MRAP2) are well-known endocrine regulators for the trafficking and signalling of all five melanocortin receptors (MC1R-MC5R). The observation of MRAP2 on regulating several non-melanocortin G protein-coupled receptors (GPCRs) has been sporadically reported, whereas other endogenous GPCR partners of the MRAP protein family are largely unknown.
methodsHere, we performed single-cell transcriptome analysis and drew a fine GPCR blueprint and MRAPs-associated network of two major endocrine organs, the hypothalamus and adrenal gland at single-cell resolution. We also integrated multiple bulk RNA-seq profiles and single-cell datasets of human and mouse tissues, and narrowed down a list of 48 GPCRs with strong endogenous co-expression correlation with MRAPs.
results36 and 46 metabolic-related GPCRs were consequently identified as novel interacting partners of MRAP1 or MRAP2, respectively. MRAPs exhibited protein-protein interactions and varying pharmacological properties on the surface translocation, constitutive activities and ligand-stimulated downstream signalling of these GPCRs. Knockdown of MRAP2 expression by hypothalamic administration of adeno-associated virus (AAV) packed shRNA stimulated body weight gain in mouse model. Co-injection of corticotropinreleasing factor (CRF), the agonist of corticotropin releasing hormone receptor 1 (CRHR1), suppressed feeding behaviour in a MRAP2-dependent manner.
conclusionsCollectively, our study has comprehensively elucidated the complex GPCR networks in two major endocrine organs and redefined the MRAP protein family as broad-spectrum GPCR modulators. MRAP proteins not only serve as a vital endocrine pivot on the regulation of global GPCR activities in vivo that could explain the composite physiological phenotypes of the MRAP2 null murine model but also provide us with new insights of the phenotyping investigation of GPCR-MRAP functional complexes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.