Cited by 199melanin and skin pigmentationAdvanced Proteomics Techniques and ApplicationsMelanoma and MAPK Pathways

Proteomic and Bioinformatic Characterization of the Biogenesis and Function of Melanosomes

Chi, An, Valencia, Julio C., Hu, Zhang-Zhi, Watabe, Hidenori, Yamaguchi, Hiroshi, Mangini, Nancy J., Huang, Hongzhan, Canfield, Victor A. +9 more·2006·Journal of Proteome Research

Abstract

Melanin, which is responsible for virtually all visible skin, hair, and eye pigmentation in humans, is synthesized, deposited, and distributed in subcellular organelles termed melanosomes. A comprehensive determination of the protein composition of this organelle has been obstructed by the melanin present. Here, we report a novel method of removing melanin that includes in-solution digestion and immobilized metal affinity chromatography (IMAC). Together with in-gel digestion, this method has allowed us to characterize melanosome proteomes at various developmental stages by tandem mass spectrometry. Comparative profiling and functional characterization of the melanosome proteomes identified approximately 1500 proteins in melanosomes of all stages, with approximately 600 in any given stage. These proteins include 16 homologous to mouse coat color genes and many associated with human pigmentary diseases. Approximately 100 proteins shared by melanosomes from pigmented and nonpigmented melanocytes define the essential melanosome proteome. Proteins validated by confirming their intracellular localization include PEDF (pigment-epithelium derived factor) and SLC24A5 (sodium/potassium/calcium exchanger 5, NCKX5). The sharing of proteins between melanosomes and other lysosome-related organelles suggests a common evolutionary origin. This work represents a model for the study of the biogenesis of lysosome-related organelles.

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Crossref · 10.1021/pr060363j

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Authors
Chi, A., Valencia, J. C., Hu, Z.-Z., Watabe, H., Yamaguchi, H., Mangini, N. J., Huang, H., Canfield, V. A., Cheng, K. C., Yang, F., Abe, R., Yamagishi, S., Shabanowitz, J., Hearing, V. J., Wu, C., Appella, E., & Hunt, D. F.
Affiliations
  • National Institutes of Health (US)
  • Department of Chemistry, University of Virginia, Charlottesville, Virginia, 22904, Laboratory of Cell Biology, National Institutes of Health, Bethesda, Maryland, 20892, Protein Information Resource, Georgetown University Medical Center, Washington, DC, Indiana University School of MedicineNorthwest, Gary, Indiana, Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, Jake Gittlen Cancer Research Foundation, Pennsylvania State University College of Medicine,...
Venue
Journal of Proteome Research
Published
2006-10-04
Volume
5
Issue
11
Pages
3135-3144
ISSN
  • 1535-3893 (ISSN-L)
  • 1535-3907
OpenAlex
W2134091914
Cited by
199
References
50
Citations by year
2026: 7 · 2025: 2 · 2024: 6 · 2023: 10 · 2022: 6 · 2021: 8 · 2020: 8 · 2019: 6 · 2018: 12 · 2017: 8 · 2016: 6 · 2015: 8 · 2014: 10 · 2013: 14 · 2012: 10
FWCI
7.18
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Proteome Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01hd040179-05)
  • National Human Genome Research Institute (U01HG02712, U01HG002712)
  • National Institute of General Medical Sciences (GM37537, R01GM037537)
  • National Center for Research Resources (RR01744)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD40179)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Keywords
melanosomes, melanin, melanosome biogenesis, melanocyte development, coat color genes, lysosome-related organelles, pigment epithelium-derived factor, SLC24A5, melanogenesis, organelle evolution
MeSH terms
Animals, Organelle Biogenesis, Chromatography, Affinity, Eye Color, Hair Color, Humans, Melanoma, Neoplasm Proteins, Peptide Fragments, Trypsin, Reproducibility of Results, Computational Biology, Melanosomes, Gene Expression Profiling, Proteomics, Cell Line, Tumor, Mice

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