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

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.

• Authors: Justin W Smith, Amy Koshoffer, Randal E Morris, Raymond E Boissy
• Journal: Pigment cell research (Pigment Cell Res) Vol. 18 Issue 6 Pg. 417-26 (Dec 2005) ISSN: 0893-5785 [Print] Denmark
• PMID: 16280007 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• MAP1LC3A protein, human
• Membrane Proteins
• Microtubule-Associated Proteins
• ribophorin
• Gold
• Monophenol Monooxygenase
• Acid Phosphatase
• Cathepsins
• Cysteine Endopeptidases
• CTSL protein, human
• Cathepsin L

Topics

• Acid Phosphatase (metabolism)
• Autophagy
• Biopsy
• Cathepsin L
• Cathepsins (metabolism)
• Cell Membrane (metabolism, ultrastructure)
• Cysteine Endopeptidases (metabolism)
• Endosomes (metabolism)
• Fluorescent Antibody Technique, Indirect
• Gold (chemistry)
• Hermanski-Pudlak Syndrome (metabolism, pathology)
• Humans
• Lysosomes (metabolism)
• Melanocytes (metabolism, ultrastructure)
• Membrane Proteins (metabolism)
• Microtubule-Associated Proteins (metabolism)
• Monophenol Monooxygenase (metabolism)
• Phagosomes (metabolism)
• Protein Transport
• Skin (metabolism)