Membranous complexes characteristic of melanocytes derived from patients with Hermansky–Pudlak syndrome type 1 are macroautophagosomal entities of the lysosomal compartment

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Abstract
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.