Improper trafficking of melanocyte-specific proteins in Hermansky-Pudlak syndrome type-5

J Invest Dermatol. 2007 Jun;127(6):1471-8. doi: 10.1038/sj.jid.5700737. Epub 2007 Feb 15.

Abstract

Hermansky-Pudlak syndrome (HPS) is a disorder of lysosome-related organelle biogenesis resulting in melanosome dysfunction and absent platelet dense bodies. HPS patients have oculocutaneous albinism, bruising, and bleeding. HPS-5 results from deficiency of the HPS5 protein, a component of the biogenesis of lysosome-related organelles complex-2 (BLOC-2). HPS5 has an unknown function and lacks homology to known proteins. We performed ultrastructural studies of HPS-5 melanocytes revealing predominantly early-stage melanosomes with many small 3,4(OH)2-phenylalanine-positive vesicles throughout the cell body and dendrites. These findings resemble the distinct ultrastructural features of HPS-3 melanocytes; HPS3 is also a BLOC-2 component. Immunofluorescence and immunoEM studies showed decreased TYRP1 labeling in the dendrites of HPS-5 melanocytes, and the overall abundance of TYRP1 was reduced. No substantial differences were observed in the distribution or abundance of Pmel17 in HPS-5 melanocytes. In normal melanocytes, endogenous tyrosinase colocalized with Pmel17 and TYRP1 in the perinuclear area and dendritic tips; this was much reduced in HPS-5 melanocytes, particularly in the tips. We conclude that early stage melanosome formation and Pmel17 trafficking are preserved in HPS5-deficient cells. Tyrosinase and TYRP1 are mistrafficked, however, and fail to be efficiently delivered to melanosomes of HPS-5 melanocytes.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Blotting, Western
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Compartmentation
  • Cells, Cultured
  • Cytoplasmic Vesicles / metabolism
  • Cytoplasmic Vesicles / ultrastructure
  • Hermanski-Pudlak Syndrome / genetics
  • Hermanski-Pudlak Syndrome / metabolism*
  • Humans
  • Melanocytes / metabolism*
  • Melanocytes / ultrastructure
  • Membrane Glycoproteins / metabolism
  • Microscopy, Electron
  • Monophenol Monooxygenase / metabolism
  • Oxidoreductases / metabolism
  • Protein Transport / physiology*

Substances

  • Carrier Proteins
  • HPS5 protein, human
  • Membrane Glycoproteins
  • Oxidoreductases
  • TYRP1 protein, human
  • Monophenol Monooxygenase