Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes

An Chi, Julio C. Valencia, Zhang Zhi Hu, Hidenori Watabe, Hiroshi Yamaguchi, Nancy J. Mangini, Hongzhan Huang, Victor A. Canfield, Keith C. Cheng, Feng Yang, Riichiro Abe, Shoichi Yamagishi, Jeffrey Shabanowitz, Vincent J. Hearing, Cathy Wu, Ettore Appella, Donald F. Hunt

Research output: Contribution to journalArticlepeer-review

163 Scopus citations


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 ∼1500 proteins in melanosomes of all stages, with ∼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 rigin. This work represents a model for the study of the biogenesis of lysosome-related organelles.

Original languageEnglish (US)
Pages (from-to)3135-3144
Number of pages10
JournalJournal of Proteome Research
Issue number11
StatePublished - Nov 2006

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • Biochemistry


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