Submission Title

Sending Mixed Signals: A Study of the Melanocortin-1-Receptor

Subject Area

Biology

Description

Skin tone varies considerably among humans across the world. These variations are due in part to different types of skin pigments known as melanin. The two main types of melanin are eumelanin and pheomelanin. Eumelanin, a brown/black pigment, is produced in response to ultraviolet radiation (UVR) and provides protection from harmful UV rays. On the other hand, pheomelanin is a red/yellow pigment and is not photoprotective. According to the World Health Organization, skin cancer is one of the most common forms of cancer. Individuals who produce predominantly pheomelanin typically have fair skin, red or blonde hair, are unable to tan, and are at greater risk for developing melanoma skin cancer. Melanoma is cancer of the pigment-producing cells known as melanocytes. UV exposure causes release of the melanocyte stimulating hormone (MSH), which activates a receptor on melanocytes called the melanocortin-1 receptor (MC1R). MSH stimulates MC1R signaling pathways which produce photoprotective eumelanin. In contrast, pheomelanin is produced when the MC1R signaling pathway is inactive. MC1R signaling is typically inactive in individuals who carry melanoma-associated MC1R variants. Two of the most frequent melanoma-associated mutations are MC1R-R151C and MC1R-D294H. Both of these mutations cause red hair, fair skin, and increased skin cancer risk. These mutations also impact surface levels of MC1R, which in turn affect the eumelanin synthesis pathway. Previous work in human embryonic kidney cells suggests that MC1R signaling is reduced in both of these mutations and that MC1R-R151C decreases MC1R surface levels, while MC1R-D294H increases MC1R surface levels. How these mutations alter MC1R localization in melanocytes is unknown. We investigated how MC1R surface levels differ among wild type MC1R and MC1R skin cancer mutants. We observed that MC1R-R151C decreases receptor surface levels and MC1R-D294H increases surface levels in mouse melanocytes.

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Sending Mixed Signals: A Study of the Melanocortin-1-Receptor

Skin tone varies considerably among humans across the world. These variations are due in part to different types of skin pigments known as melanin. The two main types of melanin are eumelanin and pheomelanin. Eumelanin, a brown/black pigment, is produced in response to ultraviolet radiation (UVR) and provides protection from harmful UV rays. On the other hand, pheomelanin is a red/yellow pigment and is not photoprotective. According to the World Health Organization, skin cancer is one of the most common forms of cancer. Individuals who produce predominantly pheomelanin typically have fair skin, red or blonde hair, are unable to tan, and are at greater risk for developing melanoma skin cancer. Melanoma is cancer of the pigment-producing cells known as melanocytes. UV exposure causes release of the melanocyte stimulating hormone (MSH), which activates a receptor on melanocytes called the melanocortin-1 receptor (MC1R). MSH stimulates MC1R signaling pathways which produce photoprotective eumelanin. In contrast, pheomelanin is produced when the MC1R signaling pathway is inactive. MC1R signaling is typically inactive in individuals who carry melanoma-associated MC1R variants. Two of the most frequent melanoma-associated mutations are MC1R-R151C and MC1R-D294H. Both of these mutations cause red hair, fair skin, and increased skin cancer risk. These mutations also impact surface levels of MC1R, which in turn affect the eumelanin synthesis pathway. Previous work in human embryonic kidney cells suggests that MC1R signaling is reduced in both of these mutations and that MC1R-R151C decreases MC1R surface levels, while MC1R-D294H increases MC1R surface levels. How these mutations alter MC1R localization in melanocytes is unknown. We investigated how MC1R surface levels differ among wild type MC1R and MC1R skin cancer mutants. We observed that MC1R-R151C decreases receptor surface levels and MC1R-D294H increases surface levels in mouse melanocytes.