Journal
PIGMENT CELL RESEARCH
Volume 18, Issue 6, Pages 417-426Publisher
WILEY
DOI: 10.1111/j.1600-0749.2005.00265.x
Keywords
macroautophagosomes; Hermansky-Pudlak syndrome; melanocytes; trafficking
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Funding
- NIAMS NIH HHS [R01 AR045429, R01 AR45429] Funding Source: Medline
- NIDDK NIH HHS [T35 DK060444] Funding Source: Medline
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Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder resulting from mutations in a family of genes required for efficient transport of lysosomal-related proteins from the trans-Golgi network to a target organelle. To date, there are several genetically distinct forms of HPS. Many forms of HPS exhibit aberrant trafficking of melanosome-targeted proteins resulting in incomplete melanosome biogenesis responsible for oculocutaneous albinism observed in patients. In HPS-1, melanosome-targeted proteins are localized to characteristic membranous complexes, which have morphologic similarities to macroautophagosomes. In this report, we evaluated the hypothesis that HPS-1-specific membranous complexes comprise a component of the lysosomal compartment of melanocytes. Using indirect immunofluorescence, an increase in co-localization of misrouted tyrosinase with cathepsin-L, a lysosomal cysteine protease, occurred in HPS-1 melanocytes. In addition, ribophorin II, an integral endoplasmic reticulum protein that is also a component of macroautophagosomes, and LC3, a specific marker of macrophagosomes, demonstrated localization to membranous complexes in HPS-1 melanocytes. At the electron microscopic level, the membranous complexes exhibited acid phosphatase activity and localization of exogenously supplied horseradish peroxidase (HRP)-conjugated gold particles, indicating incorporation of lysosomal and endosomal components to membranous complexes, respectively. These results confirm that membranous complexes of HPS-1 melanocytes are macroautophagosomal representatives of the lysosomal compartment.
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