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PMID: 16492709 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

Sorting of Pmel17 to melanosomes through the plasma membrane by AP1 and AP2: evidence for the polarized nature of melanocytes.

Journal of cell science ·Vol. 119 ·No. Pt 6 ·2006-03-15 ·Pages 1080-91

Valencia JC, Watabe H, Chi A, Rouzaud F, Chen KG, Vieira WD, Takahashi K, Yamaguchi Y, Berens W, Nagashima K, Shabanowitz J, Hunt DF, Appella E, Hearing VJ

Abstract

Adaptor proteins (AP) play important roles in the sorting of proteins from the trans-Golgi network, but how they function in the sorting of various melanosome-specific proteins such as Pmel17, an essential structural component of melanosomes, in melanocytes is unknown. We characterized the processing and trafficking of Pmel17 via adaptor protein complexes within melanocytic cells. Proteomics analysis detected Pmel17, AP1 and AP2, but not AP3 or AP4 in early melanosomes. Real-time PCR, immunolabeling and tissue in-situ hybridization confirmed the coexpression of AP1 isoforms mu1A and mu1B (expressed only in polarized cells) in melanocytes and keratinocytes, but expression of mu1B is missing in some melanoma cell lines. Transfection with AP1 isoforms (mu1A or mu1B) showed two distinct distribution patterns that involved Pmel17, and only mu1B was able to restore the sorting of Pmel17 to the plasma membrane in cells lacking mu1B expression. Finally, we established that expression of mu1B is regulated physiologically in melanocytes by UV radiation or DKK1. These results show that Pmel17 is sorted to melanosomes by various intracellular routes, directly or indirectly through the plasma membrane, and the presence of basolateral elements in melanocytes suggests their polarized nature.

MeSH Terms
Adaptor Protein Complex 1/genetics,metabolism Adaptor Protein Complex 2/genetics,metabolism Cell Line, Tumor Cell Membrane/metabolism Cell Polarity Humans Melanocytes/metabolism,ultrastructure Melanosomes/metabolism Membrane Glycoproteins/metabolism Microscopy, Electron Protein Subunits/genetics,metabolism Protein Transport Skin/metabolism gp100 Melanoma Antigen
Chemicals
Adaptor Protein Complex 1 Adaptor Protein Complex 2 Membrane Glycoproteins PMEL protein, human Protein Subunits gp100 Melanoma Antigen
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Valencia Julio C
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Watabe Hidenori
Chi An
Rouzaud Francois
Chen Kevin G
Vieira Wilfred D
Takahashi Kaoruko
Yamaguchi Yuji
Berens Werner
Nagashima Kunio
Shabanowitz Jeffrey
Hunt Donald F
Appella Ettore
Hearing Vincent J
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Article Info
Journal
Journal of cell science
Abbr.
J Cell Sci
ISSN
0021-9533
DOI
10.1242/jcs.02804
Published
2006-03-15
Epub
2006-00-21
Pages
1080-91
Language
English
Region
England
NLM ID
0052457
PMCID
PMC4629779
Subset
IM
Grants
NIGMS NIH HHS · R01 GM037537 · United States
Intramural NIH HHS · Z99 NS999999 · United States
NIGMS NIH HHS · GM 37537 · United States
External Links
PubMed source DOI: 10.1242/jcs.02804 PMC Full Text View journal details
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