MC1R Functions, Expression, and Implications for Targeted Therapy

J Invest Dermatol. 2022 Feb;142(2):293-302.e1. doi: 10.1016/j.jid.2021.06.018. Epub 2021 Aug 4.

Abstract

The G protein-coupled MC1R is expressed in melanocytes and has a pivotal role in human skin pigmentation, with reduced function in human genetic variants exhibiting a red hair phenotype and increased melanoma predisposition. Beyond its role in pigmentation, MC1R is increasingly recognized as promoting UV-induced DNA damage repair. Consequently, there is mounting interest in targeting MC1R for therapeutic benefit. However, whether MC1R expression is restricted to melanocytes or is more widely expressed remains a matter of debate. In this paper, we review MC1R function and highlight that unbiased analysis suggests that its expression is restricted to melanocytes, granulocytes, and the brain.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • DNA Damage / radiation effects
  • DNA Repair
  • Disease Models, Animal
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Granulocytes / metabolism
  • Hair Color
  • Humans
  • Lipoylation / drug effects
  • Loss of Function Mutation
  • Melanins / metabolism
  • Melanocytes / metabolism
  • Melanoma / genetics*
  • Melanoma / pathology
  • Mice
  • Molecular Targeted Therapy / methods
  • Receptor, Melanocortin, Type 1 / agonists
  • Receptor, Melanocortin, Type 1 / genetics
  • Receptor, Melanocortin, Type 1 / metabolism*
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Skin Pigmentation
  • Ultraviolet Rays / adverse effects

Substances

  • MC1R protein, human
  • Melanins
  • Receptor, Melanocortin, Type 1