Membrane-Associated Transporter Protein (MATP) Regulates Melanosomal pH and Influences Tyrosinase Activity

PLoS One. 2015 Jun 9;10(6):e0129273. doi: 10.1371/journal.pone.0129273. eCollection 2015.

Abstract

The SLC45A2 gene encodes a Membrane-Associated Transporter Protein (MATP). Mutations of this gene cause oculocutaneous albinism type 4 (OCA4). However, the molecular mechanism of its action in melanogenesis has not been elucidated. Here, we discuss the role of MATP in melanin production. The SLC45A2 gene is highly enriched in human melanocytes and melanoma cell lines, and its protein, MATP, is located in melanosomes. The knockdown of MATP using siRNAs reduced melanin content and tyrosinase activity without any morphological change in melanosomes or the expression of melanogenesis-related proteins. Interestingly, the knockdown of MATP significantly lowered the melanosomal pH, as verified through DAMP analysis, suggesting that MATP regulates melanosomal pH and therefore affects tyrosinase activity. Finally, we found that the reduction of tyrosinase activity associated with the knockdown of MATP was readily recovered by copper treatment in the in vitro L-DOPA oxidase activity assay of tyrosinase. Considering that copper is an important element for tyrosinase activity and that its binding to tyrosinase depends on melanosomal pH, MATP may play an important role in regulating tyrosinase activity via controlling melanosomal pH.

MeSH terms

  • Antigens, Neoplasm / metabolism*
  • Cell Line, Tumor
  • Humans
  • Hydrogen-Ion Concentration
  • Indoles / metabolism
  • Melanins / metabolism
  • Melanocytes / metabolism
  • Melanoma / metabolism
  • Melanosomes / metabolism*
  • Membrane Proteins / metabolism
  • Membrane Transport Proteins / metabolism*
  • Monophenol Monooxygenase / metabolism*
  • Mutation / genetics
  • Oxidation-Reduction

Substances

  • Antigens, Neoplasm
  • Indoles
  • Melanins
  • Membrane Proteins
  • Membrane Transport Proteins
  • SLC45A2 protein, human
  • melanogen
  • Monophenol Monooxygenase

Grant support

Amorepacific Corporation R&D Center provided support in the form of salaries for authors BHB, SHY, MS, DWS, EGC and TRL, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.