Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes.

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Chi A, Valencia JC, Hu ZZ, Watabe H, Yamaguchi H, Mangini NJ, Huang H, Canfield VA, Cheng KC, Yang F, Abe R, Yamagishi S, Shabanowitz J, Hearing VJ, Wu C, Appella E, Hunt DF

Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes.

J Proteome Res. 2006 Nov;5(11):3135-44.

PubMed ID
17081065 [ View in PubMed
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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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Neutral amino acid transporter B(0)Q15758Details
TyrosinaseP14679Details
Gamma-glutamyl hydrolaseQ92820Details
Neutral amino acid transporter AP43007Details
Sodium/potassium-transporting ATPase subunit alpha-1P05023Details
Cathepsin BP07858Details
Cathepsin DP07339Details
Fatty acid synthaseP49327Details
CalnexinP27824Details
Solute carrier family 2, facilitated glucose transporter member 1P11166Details
Endoplasmic reticulum chaperone BiPP11021Details
Ras-related C3 botulinum toxin substrate 1P63000Details
Heat shock protein HSP 90-alphaP07900Details
EndoplasminP14625Details
Annexin A2P07355Details
14-3-3 protein zeta/deltaP63104Details
AdenosylhomocysteinaseP23526Details
Heat shock protein HSP 90-betaP08238Details
Peptidyl-prolyl cis-trans isomerase BP23284Details
Protein disulfide-isomeraseP07237Details
Transmembrane glycoprotein NMBQ14956Details
Integrin beta-1P05556Details
Matrix metalloproteinase-14P50281Details
Heat shock cognate 71 kDa proteinP11142Details
V-type proton ATPase subunit B, brain isoformP21281Details
Ras-related protein Rab-7aP51149Details
Myosin-11P35749Details
Ras-related protein Rab-5AP20339Details
GTP-binding nuclear protein RanP62826Details
14-3-3 protein epsilonP62258Details
Neutral alpha-glucosidase ABQ14697Details
Transferrin receptor protein 1P02786Details
Sodium/potassium-transporting ATPase subunit beta-3P54709Details
Peroxiredoxin-1Q06830Details
14-3-3 protein beta/alphaP31946Details
Protein disulfide-isomerase A3P30101Details
Pigment epithelium-derived factorP36955Details
Transient receptor potential cation channel subfamily V member 2Q9Y5S1Details
V-type proton ATPase 116 kDa subunit a 1Q93050Details
V-type proton ATPase subunit G 2O95670Details
Melanocyte protein PMELP40967Details