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Glycoprotein nonmetastatic melanoma protein b, a melanocytic cell marker, is a melanosome‐specific and proteolytically released protein
Author(s) -
Hoashi Toshihiko,
Sato Shinichi,
Yamaguchi Yuji,
Passeron Thierry,
Tamaki Kunihiko,
Hearing Vincent J.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-151019
Subject(s) - melanosome , ectodomain , microbiology and biotechnology , biology , melanin , melanocyte , glycoprotein , melanoma , organelle , golgi apparatus , endoplasmic reticulum , cancer research , biochemistry , receptor
Melanosomes are organelles specialized for the production of melanin pigment and are specifically produced by melanocytic cells. More than 150 pigmentation‐related genes have been identified, including glycoprotein nonmetastatic melanoma protein b (GPNMB). A recent proteomics analysis revealed that GPNMB is localized in melanosomes, and GPNMB is a membrane‐bound glycoprotein that shows high homology with a well‐known melanosomal structural protein, Pmel17/gp100. In this study, we show that GPNMB is expressed in melanocytes of normal human skin, as well as in human melanoma cells. GPNMB is heavily glycosylated and is enriched in mature (stage III and IV) melanosomes in contrast to MART‐1 and Pmel17, which are abundant in early (stage I and II) melanosomes. MART‐1 and Pmel17 play critical roles in the maturation of early melanosomes; thus, we speculate that GPNMB might be important in the functions of late melanosomes, possibly their transport and/or transfer to keratinocytes. We also demonstrate that a secreted form of GPNMB is released by ectodomain shedding from the largely Golgi‐modified form of GPNMB and that the PKC and Ca 2+ intracellular signaling pathways regulate that shedding. We conclude that GPNMB is a melanosomal protein that is released by proteolytic ectodomain shedding and might be a useful and specific histological marker of melanocytic cells.—Hoashi, T., Sato, S., Yamaguchi, Y., Passeron, T., Tamaki, K., Hearing, V. J. Glycoprotein nonmetastatic melanoma protein b, a melanocytic cell marker, is a melanosome‐specific and proteolytically released protein. FASEB J. 24, 1616–1629 (2010). www.fasebj.org