Mislocalization of melanosomal proteins in melanocytes from mice with oculocutaneous albinism type 2

Exp Eye Res. 2001 Jun;72(6):695-710. doi: 10.1006/exer.2001.1006.


More than 10% of admissions worldwide to institutions for the visually impaired are due to some form of albinism. The most common form, oculocutaneous albinism type 2, results from mutations at the p locus. The function of the p gene is yet to be determined. It has been shown that melanocytes from p -null mice exhibit an abnormal melanosomal ultrastructure in addition to alterations in activity and localization of tyrosinase, a critical melanogenic enzyme. In light of these observations, we examined tyrosinase trafficking in p -null vs wildtype mouse melanocytes in order to explore p function. Electron microscopy of wildtype melan-a and p -null melan-p1 cells demonstrated accumulation of tyrosinase in 50 nm vesicles throughout the cell in the absence of p, an observation corroborated by an increase in tyrosinase activity in vesicle-enriched fractions from melan-p1 compared to melan-a cells. Misrouting in the absence of p was not limited to tyrosinase; a second melanosomal protein, tyrosinase-related protein 1, also trafficked incorrectly. In melan-p1, mislocalization led to secretion of tyrosinase into the medium. Adding tyrosine to the medium was found to partially correct tyrosinase trafficking and to reduce secretion; the cysteine protease inhibitor E64 also reduced secretion. We propose that p is required by melanocytes for transport of melanosomal proteins. In its absence, tyrosinase accumulates in vesicles and, in cultured melanocytes, is proteolysed and secreted.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Albinism, Oculocutaneous / metabolism*
  • Albinism, Oculocutaneous / pathology
  • Animals
  • Cells, Cultured
  • Electrophoresis, Polyacrylamide Gel
  • Golgi Apparatus / metabolism
  • Hydrolysis
  • Melanocytes / metabolism*
  • Melanocytes / ultrastructure
  • Melanosomes / metabolism*
  • Melanosomes / ultrastructure
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron
  • Monophenol Monooxygenase / metabolism


  • Monophenol Monooxygenase