ArticleThe Journal of biological chemistry2011
Mahoganoid and mahogany mutations rectify the obesity of the yellow mouse by effects on endosomal traffic of MC4R protein.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- MGRN1 in development and disease: a unifying view of a versatile membrane-tethered E3 ubiquitin ligase.Biochemical Society transactions · 2026Review
- The role of accessory proteins and co-factors in regulation of melanocortin-4 receptor signalling: An update.Journal of neuroendocrinology · 2026Review
- The E3 ubiquitin ligase MGRN1 targets melanocortin receptors MC1R and MC4R via interactions with transmembrane adapters.Journal of cell science · 2025Article
- Concurrent outcomes from multiple approaches of epistasis analysis for human body mass index associated loci provide insights into obesity biology.Scientific reports · 2022Article
- Receptor control by membrane-tethered ubiquitin ligases in development and tissue homeostasis.Current topics in developmental biology · 2022Article
- Mahogunin Ring Finger 1 Is Required for Genomic Stability and Modulates the Malignant Phenotype of Melanoma Cells.Cancers · 2020Article
- The melanocortin pathway and control of appetite-progress and therapeutic implications.The Journal of endocrinology · 2019Review
- The Drosophila homologue of MEGF8 is essential for early development.Scientific reports · 2018Article
- CRISPR Screens Uncover Genes that Regulate Target Cell Sensitivity to the Morphogen Sonic Hedgehog.Developmental cell · 2018Article
- Agouti Signaling Protein and Its Receptors as Potential Molecular Markers for Intramuscular and Body Fat Deposition in Cattle.Frontiers in physiology · 2018Article
- Role of the E3 ubiquitin ligase RNF157 as a novel downstream effector linking PI3K and MAPK signaling pathways to the cell cycle.The Journal of biological chemistry · 2017Article
- Alkbh4 and Atrn Act Maternally to Regulate Zebrafish Epiboly.International journal of biological sciences · 2017Article
- 60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH.Journal of molecular endocrinology · 2016Review
- The brain melanocortin system, sympathetic control, and obesity hypertension.Physiology (Bethesda, Md.) · 2014Review
- Exposure of MC4R to agonist in the endoplasmic reticulum stabilizes an active conformation of the receptor that does not desensitize.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Functional conservation between mammalian MGRN1 and plant LOG2 ubiquitin ligases.FEBS letters · 2013Article
- MGRN1-dependent pigment-type switching requires its ubiquitination activity but not its interaction with TSG101 or NEDD4.Pigment cell & melanoma research · 2013Article
- Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization.American journal of human genetics · 2012Article
- Neuronal expression of Fig4 is both necessary and sufficient to prevent spongiform neurodegeneration.Human molecular genetics · 2012Article
- Constitutive cholesterol-dependent endocytosis of melanocortin-4 receptor (MC4R) is essential to maintain receptor responsiveness to α-melanocyte-stimulating hormone (α-MSH).The Journal of biological chemistry · 2012Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The ubiquitous overexpression of agouti-signaling protein (ASP), a paracrine-signaling molecule that regulates pigment-type switching in the hair follicle of the mouse, is responsible for the obesity and yellow pelage of the Yellow mouse (A(y)). Mahogany (Attractin, Atrn/mg) and mahoganoid (Mahogunin Ring Finger-1, Mgrn1/md) are mutations epistatic to A(y). These mutations have been described as suppressors of ASP action, blocking its antagonizing effects on the melanocortin 1 and 4 receptors (MC1R and MC4R) in the skin and the brain, respectively, via unknown mechanisms. Here, we describe the molecular bases for the md- and mg-dependent rescue of the A(y) phenotype at the MC4R. We show that overexpression of ASP inhibits the rise in cAMP levels in response to α-melanocyte-stimulating hormone, an MC4R agonist, by blocking ligand binding and by directing MC4R trafficking to the lysosome. Loss-of-function of either attractin or MGRN1 blocks ASP-dependent MC4R degradation and promotes increased trafficking of internalized MC4R to the cell surface, but it does not restore α-melanocyte-stimulating hormone-dependent cAMP signaling. We propose that MGRN1 and attractin are components of an evolutionarily conserved receptor trafficking pathway and that the md and mg mutations rescue the A(y) phenotypes by a primarily cAMP-independent mechanism promoting trafficking of MC4R and likely MC1R away from the lysosome toward the cell surface.
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