ArticleJournal of cellular physiology2009
Aberrant trafficking of human melanocortin 1 receptor variants associated with red hair and skin cancer: Steady-state retention of mutant forms in the proximal golgi.
Article in Journal of cellular physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- Distinct cAMP Signaling Microdomains Differentially Regulate Melanosomal pH and Pigmentation.The Journal of investigative dermatology · 2023Article
- Therapeutic senescence via GPCR activation in synovial fibroblasts facilitates resolution of arthritis.Nature communications · 2020Article
- ACTH Receptor (MC2R) Specificity: What Do We Know About Underlying Molecular Mechanisms?Frontiers in endocrinology · 2017Review
- How Genes Modulate Patterns of Aging-Related Changes on the Way to 100: Biodemographic Models and Methods in Genetic Analyses of Longitudinal Data.North American actuarial journal : NAAJ · 2016Article
- Significance of the Melanocortin 1 and Endothelin B Receptors in Melanocyte Homeostasis and Prevention of Sun-Induced Genotoxicity.Frontiers in genetics · 2016Review
- Identification and functional characterization of natural human melanocortin 1 receptor mutant alleles in Pakistani population.Pigment cell & melanoma research · 2015Article
- MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project.British journal of cancer · 2015Article
- Functional Characterization of MC1R-TUBB3 Intergenic Splice Variants of the Human Melanocortin 1 Receptor.PloS one · 2015Article
- A naturally occurring GIP receptor variant undergoes enhanced agonist-induced desensitization, which impairs GIP control of adipose insulin sensitivity.Molecular and cellular biology · 2014Article
- MC1R, the cAMP pathway, and the response to solar UV: extending the horizon beyond pigmentation.Pigment cell & melanoma research · 2014Review
- Transitioning pharmacoperones to therapeutic use: in vivo proof-of-principle and design of high throughput screens.Pharmacological research · 2014Review
- Modeling MC1R rare variants: a structural evaluation of variants detected in a Mediterranean case-control study.The Journal of investigative dermatology · 2014Article
- Capturing the biological impact of CDKN2A and MC1R genes as an early predisposing event in melanoma and non melanoma skin cancer.Oncotarget · 2014Article
- A large French case-control study emphasizes the role of rare Mc1R variants in melanoma risk.BioMed research international · 2014Article
- The angiotensin II type 1 receptor C-terminal Lys residues interact with tubulin and modulate receptor export trafficking.PloS one · 2013Article
- Susceptibility to Cutaneous Squamous Cell Carcinoma in Renal Transplant Recipients Associates with Genes Regulating Melanogenesis Independent of their Role in Pigmentation.Biomarkers in cancer · 2013Article
- Rab26 modulates the cell surface transport of α2-adrenergic receptors from the Golgi.The Journal of biological chemistry · 2012Article
- Gain of glycosylation: a new pathomechanism of myelin protein zero mutations.Annals of neurology · 2012Article
- Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The melanocortin 1 receptor (MC1R), a Gs protein-coupled receptor (GPCR) expressed in melanocytes, is a major determinant of skin pigmentation and phototype. MC1R activation stimulates melanogenesis and increases the ratio of black, strongly photoprotective eumelanins to reddish, poorly photoprotective pheomelanins. Several MC1R alleles are associated with red hair, fair skin, increased sensitivity to ultraviolet radiation (the RHC phenotype) and increased skin cancer risk. Three highly penetrant RHC variants, R151C, R160W, and D294H are loss-of-function MC1R mutants with altered cell surface expression. In this study, we show that forward trafficking was normal for D294H. Conversely, export traffic was impaired for R151C, which accumulated in the endoplasmic reticulum (ER), and for R160W, which was enriched in the cis-Golgi. This is the first report of steady-state retention in a post-ER secretory compartment of a GPCR mutant found in the human population. Residues R151 and R160 are located in the MC1R second intracellular loop (il2). Two other mutations in il2, T157A preventing T157 phosphorylation and R162P disrupting a (160)RARR(163) motif, also caused intracellular retention. Moreover, T157 was phosphorylated in wild-type MC1R and a T157D mutation mimicking constitutive phosphorylation allowed normal traffic, and rescued the retention phenotype of R160W and R162P. Therefore, MC1R export is likely regulated by T157 phosphorylation and the (160)RARR(163) arginine-based motif functions as an ER retrieval signal. These elements are conserved in mammalian MC1Rs and in all five types of human melanocortin receptors. Thus, members of this GPCR subfamily might share common mechanisms for regulation of plasma membrane expression.
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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 OpenQuestion graph.