Poster presentation, P136

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Glycoprotein nonmetastatic melanoma protein b (GPNMB) is a melanosome-specific cell marker and is proteolytically released by ectodomain shedding

Melanosomes are organelles specialized for the production of melanin pigment and are specific to melanocytic cells. More than 150 pigmentation-related genes that associated with pigmentation have been identified to date, 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 which shows high homology with a well-known melanosomal structural protein, Pmel17/gp100. In this study, we show that GPNMB is predominantly expressed in melanocytes of normal human skin as well as in human melanoma cells, even in amelanotic melanoma cells. GPNMB is heavily glycosylated and is enriched in Stage III and IV melanosomes. We also demonstrate that a secreted form of GPNMB is released by ectodomain shedding from the largely Golgi-modified form of GPNMB and that a phorbol ester or a calmodulin inhibitor induces the shedding. We conclude that GPNMB is a melanosomal protein that can be released by regulated proteolytic ectodomain shedding.

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