Functional Characterization of the Odorant Receptor 51E2 in Human Melanocytes

J Biol Chem. 2016 Aug 19;291(34):17772-86. doi: 10.1074/jbc.M116.734517. Epub 2016 May 18.

Abstract

Olfactory receptors, which belong to the family of G-protein-coupled receptors, are found to be ectopically expressed in non-sensory tissues mediating a variety of cellular functions. In this study we detected the olfactory receptor OR51E2 at the transcript and the protein level in human epidermal melanocytes. Stimulation of primary melanocytes with the OR51E2 ligand β-ionone significantly inhibited melanocyte proliferation. Our results further showed that β-ionone stimulates melanogenesis and dendritogenesis. Using RNA silencing and receptor antagonists, we demonstrated that OR51E2 activation elevated cytosolic Ca(2+) and cAMP, which could mediate the observed increase in melanin synthesis. Co-immunocytochemical stainings using a specific OR51E2 antibody revealed subcellular localization of the receptor in early endosomes associated with EEA-1 (early endosome antigen 1). Plasma membrane preparations showed that OR51E2 protein is present at the melanocyte cell surface. Our findings thus suggest that activation of olfactory receptor signaling by external compounds can influence melanocyte homeostasis.

Keywords: G protein-coupled receptor (GPCR); calcium imaging; cell differentiation; cell proliferation; cell signaling.

MeSH terms

  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Cell Line
  • Cell Membrane / metabolism*
  • Cyclic AMP / metabolism
  • Endosomes / metabolism
  • Epidermal Cells
  • Epidermis / metabolism*
  • Humans
  • Melanocytes / cytology
  • Melanocytes / metabolism*
  • Neoplasm Proteins / metabolism*
  • Norisoprenoids / pharmacology
  • Receptors, Odorant / metabolism*
  • Vesicular Transport Proteins / metabolism

Substances

  • Neoplasm Proteins
  • Norisoprenoids
  • OR51E2 protein, human
  • Receptors, Odorant
  • Vesicular Transport Proteins
  • early endosome antigen 1
  • beta-ionone
  • Cyclic AMP
  • Calcium