Gpnmb is a melanosome-associated glycoprotein that contributes to melanocyte/keratinocyte adhesion in a RGD-dependent fashion

Mizuki Tomihari, Sun Hee Hwang, Jin Sung Chung, Ponciano D Cruz, Kiyoshi Ariizumi

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Gpnmb is a glycosylated transmembrane protein implicated in the development of glaucoma in mice and melanoma in humans. It shares significant amino acid sequence homology with the melanosome protein Pmel-17. Its extracellular domain contains a RGD motif for binding to integrin and its intracellular domain has a putative endosomal and/or melanosomal-sorting motif. These features led us to posit that Gpnmb is associated with melanosomes and involved in cell adhesion. We showed that human Gpnmb is expressed constitutively by melanoma cell lines, primary-cultured melanocytes and epidermal melanocytes in situ, with most of it found intracellularly within melanosomes and to a lesser degree in lysosomes. Our newly developed monoclonal antibody revealed surface expression of Gpnmb on these pigment cells, albeit to a lesser degree than the intracellular fraction. Gpnmb expression was upregulated by UVA (but not UVB) irradiation and by α-melanocyte-stimulating hormone (MSH) (but not β-MSH); its cell surface expression on melanocytes (but not on melanoma cells) was increased markedly by IFN-γ and TNF-α. PAM212 keratinocytes adhered to immobilized Gpnmb in a RGD-dependent manner. These results indicate that Gpnmb is a melanosome-associated glycoprotein that contributes to the adhesion of melanocytes with keratinocytes.

Original languageEnglish (US)
Pages (from-to)586-595
Number of pages10
JournalExperimental Dermatology
Volume18
Issue number7
DOIs
StatePublished - Jun 17 2009

Keywords

  • Adhesion
  • Gpnmb
  • Keratinocytes
  • Melanocytes
  • Melanoma

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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