Jun 24, 2005

Altered cell surface expression of human MC1R variant receptor alleles associated with red hair and skin cancer risk

Human Molecular Genetics
Kimberley A BeaumontRichard A Sturm

Abstract

The human melanocortin-1 receptor gene (MC1R) encodes a G-protein coupled receptor that is primarily expressed on melanocytes, where it plays a key role in pigmentation regulation. Variant alleles are associated with red hair colour and fair skin, known as the RHC phenotype, as well as skin cancer risk. The R151C, R160W and D294H alleles, designated 'R', are strongly associated with the RHC phenotype and have been proposed to result in loss of function receptors due to impaired G-protein coupling. We recently provided evidence that the R151C and R160W variants can efficiently couple to G-proteins in response to alpha-melanocyte stimulating hormone. The possibility that altered cellular localization of the R151C and R160W variant receptors could underlie their association with RHC was therefore considered. Using immunofluorescence and ligand binding studies, we found that melanocytic cells exogenously or endogenously expressing MC1R show strong surface localization of the wild-type and D294H alleles but markedly reduced cell surface expression of the R151C and R160W receptors. In additional exogenous expression studies, the R variant D84E and the rare I155T variant, also demonstrated a significant reduction in plasma membrane re...Continue Reading

  • References42
  • Citations92

Mentioned in this Paper

Malignant Neoplasm of Skin
Establishment and Maintenance of Localization
Immunofluorescence Assay
Melanocyte
Transfection
MC1R Protein
Ligand Binding
G-Protein-Coupled Receptors
Corticotropin Receptors
Receptors, Cell Surface

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