MART-1 is required for the function of the melanosomal matrix protein PMEL17/GP100 and the maturation of melanosomes

J Biol Chem. 2005 Apr 8;280(14):14006-16. doi: 10.1074/jbc.M413692200. Epub 2005 Jan 28.

Abstract

More than 125 genes that regulate pigmentation have been identified to date. Of those, MART-1 has been widely studied as a melanoma-specific antigen and as a melanosome-specific marker. Whereas the functions of other melanosomal proteins, such as tyrosinase, tyrosinase-related protein-1, dopachrome tautomerase, and Pmel17, are known, the function of MART-1 in melanogenesis, is unclear. A role for MART-1 in pigmentation is expected because its expression pattern and subcellular distribution is quite similar to the other melanosomal proteins and usually correlates with melanin content. We investigated the function of MART-1 using a multidisciplinary approach, including the use of siRNA to inhibit MART-1 function and the use of transfection to re-express MART-1 in MART-1-negative cells. We show that MART-1 forms a complex with Pmel17 and affects its expression, stability, trafficking, and the processing which is required for melanosome structure and maturation. We conclude that MART-1 is indispensable for Pmel17 function and thus plays an important role in regulating mammalian pigmentation.

MeSH terms

  • Animals
  • Antigens, Neoplasm
  • Cell Line
  • Endoplasmic Reticulum / metabolism
  • Golgi Apparatus / metabolism
  • Humans
  • MART-1 Antigen
  • Melanoma / metabolism
  • Melanosomes / physiology*
  • Melanosomes / ultrastructure
  • Membrane Glycoproteins
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Pigmentation / physiology
  • Protein Transport
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Subcellular Fractions / metabolism
  • gp100 Melanoma Antigen

Substances

  • Antigens, Neoplasm
  • MART-1 Antigen
  • MLANA protein, human
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • PMEL protein, human
  • Proteins
  • RNA, Small Interfering
  • gp100 Melanoma Antigen