Gpnmb is a melanosome-associated glycoprotein that contributes to melanocyte/keratinocyte adhesion in a RGD-dependent fashion
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Roles for GPNMB have been described for melanocytes, melanoma, and the pigmented iris in mammals, and it has been suggested to act both as a plasma membrane protein and a component of the melanosome.
“Roles for GPNMB have been described for melanocytes, melanoma, and the pigmented iris in mammals, and it has been suggested to act both as a plasma membrane protein and a component of the melanosome [70].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
RGD AND OTHER RECOGNITION SEQUENCES FOR INTEGRINS
Ruoslahti, E. (1996) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.12.1.697 · Cited by 3,191 · see citing works
Melanocyte biology and skin pigmentation
Lin, J. Y., & Fisher, D. E. (2007) · Nature · doi:10.1038/nature05660 · Cited by 1,379 · see citing works
Flagged first, then by citations
Research works printed but not linked: 36
- [1]Shikano S Bonkobara M Zukas PK Ariizumi K Molecular cloning of a dendritic cell-associated transmembrane protein, DC-HIL, that promotes RGD-dependent adhesion of endothelial cells through recognition of heparan sulfate proteoglycans J Biol Chem 2001 276 8125 8134 11114299
- [2]Weterman MA Ajubi N van Dinter I nmb, a novel gene, is expressed in low-metastatic human melanoma cell lines and xenografts Int J Cancer 1995 60 73 81 7814155
- [3]Anderson MG Smith RS Hawes NL Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice Nat Genet 2002 30 81 85 11743578
- [4]Safadi FF Xu J Smock SL Cloning and characterization of osteoactivin, a novel cDNA expressed in osteoblasts J Cell Biol 2001 84 12 26 11746512
- [5]Metz RL Patel PS Hameed M Role of human HGFIN/nmb in breast cancer Breast Cancer Res 2007 9 R58 17845721 PMC2242655
- [7]Bycroft M Bateman A Clarke J The structure of a PKD domain from polycystin-1: implications for polycystic kidney disease EMBO J 1999 18 297 305 9889186 PMC1171124
- [8]Ponting CP Hofmann K Bork P A latrophilin/CL-1-like GPS domain in polycystin-1 Curr Biol 1999 9 R585 R588 10469603
- [9]Strzelecka A Kwiatkowska K Sobota A Tyrosine phosphorylation and Fc gamma receptor-mediated phagocytosis FEBS Lett 1997 400 11 14 9000504
- [10]Bonifacino JS Traub LM Signals for sorting of transmembrane proteins to endosomes and lysosomes Annu Rev Biochem 2003 72 395 447 12651740
- [11]Le Borgne R Planque N Martin P The AP-3-dependent targeting of the melanosomal glycoprotein QNR-71 requires a di-leucine-based sorting signal J Cell Sci 2001 114 2831 2841 11683416
- [12]Theos AC Berson JF Theos SC Dual loss of ER export and endocytic signals with altered melanosome morphology in the silver mutation of Pmel17 Mol Biol Cell 2006 17 3598 3612 16760433 PMC1525253
- [13]Chung JS Sato K Dougherty I DC-HIL is a negative regulator of T lymphocyte activation Blood 2007 109 4320 4327 17284525 PMC1885497
- [14]Chung JS Dougherty I Cruz PD Jr Ariizumi K Syndecan-4 mediates the coinhibitory function of DC-HIL on T cell activation J Immunol 2007 179 5778 5784 17947650
- [15]Sato K Shikano S Xia G Selective expression of vacuolar H+-ATPase subunit d2 by particular subsets of dendritic cells among leukocytes Mol Immunol 2006 43 1443 1453 16144709
- [16]Inaba K Inaba M Romani N Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor J Exp Med 1992 176 1693 1702 1460426 PMC2119469
- [17]Araki K Horikawa T Chakraborty AK Small Gtpase rab3A is associated with melanosomes in melanoma cells Pigment Cell Res 2000 13 332 336 11041209
- [18]Bonkobara M Yagihara H Yudate T Ultraviolet B Radiation Upregulates Expression of Dectin-2 on Epidermal Langerhans Cells by Activating the Gene Promoter Photochem Photobiol 2005 81 944 948 15876128
- [19]King R Weilbaecher KN McGill G Microphthalmia transcription factor. A sensitive and specific melanocyte marker for MelanomaDiagnosis Am J Pathol 1999 155 731 738 10487831 PMC1866880
- [20]Geuze HJ The role of endosomes and lysosomes in MHC class II functioning Immunol Today 1998 19 282 287 9639994
- [21]Krasagakis K Garbe C Zouboulis CC Orfanos CE Growth control of melanoma cells and melanocytes by cytokines Recent Results Cancer Res 1995 139 169 182 7597288
- [22]Engvall E Ruoslahti E Binding of soluble form of fibroblast surface protein, fibronectin, to collagen Int J Cancer 1977 20 1 5 903179
- [23]Ruoslahti E Pierschbacher MD New perspectives in cell adhesion: RGD and integrins Science 1987 238 491 497 2821619
- [24]Bachner D Schroder D Gross G mRNA expression of the murine glycoprotein (transmembrane) nmb (Gpnmb) gene is linked to the developing retinal pigment epithelium and iris Brain Res Gene Expr Patterns 2002 1 159 165 12638126
- [25]De LM Pellegrini G Zambruno G Marchisio PC Role of integrins in cell adhesion and polarity in normal keratinocytes and human skin pathologies J Dermatol 1994 21 821 828 7852642
- [26]Schallreuter KU Kothari S Chavan B Spencer JD Regulation of melanogenesis--controversies and new concepts Exp Dermatol 2008 17 395 404 18177348
- [27]Calvo PA Frank DW Bieler BM A cytoplasmic sequence in human tyrosinase defines a second class of di-leucine-based sorting signals for late endosomal and lysosomal delivery J Biol Chem 1999 274 12780 12789 10212263
- [28]Simmen T Schmidt A Hunziker W Beermann F The tyrosinase tail mediates sorting to the lysosomal compartment in MDCK cells via a di-leucine and a tyrosine-based signal J Cell Sci 1999 112 Pt 1 45 43 9841903
- [29]Lepage S Lapointe R Melanosomal targeting sequences from gp100 are essential for MHC class II-restricted endogenous epitope presentation and mobilization to endosomal compartments Cancer Res 2006 66 2423 2432 16489049
- [30]Hearing VJ Biogenesis of pigment granules: a sensitive way to regulate melanocyte function J Dermatol Sci 2005 37 3 14 15619429
- [31]Valencia JC Watabe H Chi A Sorting of Pmel17 to melanosomes through the plasma membrane by AP1 and AP2: evidence for the polarized nature of melanocytes J Cell Sci 2006 119 1080 1091 16492709 PMC4629779
- [32]Raposo G Marks MS Melanosomes--dark organelles enlighten endosomal membrane transport Nat Rev Mol Cell Biol 2007 8 786 797 17878918 PMC2786984
- [33]Harper DC Theos AC Herman KE Premelanosome amyloid-like fibrils are composed of only golgi-processed forms of Pmel17 that have been proteolytically processed in endosomes J Biol Chem 2008 283 2307 2322 17991747 PMC2430631
- [34]Tang A Eller MS Hara M E-cadherin is the major mediator of human melanocyte adhesion to keratinocytes in vitro J Cell Science 1994 107 983 992 8056851
- [35]Haass NK Smalley KS Li L Herlyn M Adhesion, migration and communication in melanocytes and melanoma Pigment Cell Res 2005 18 150 159 15892711
- [36]O'Toole EA Extracellular matrix and keratinocyte migration Clin Exp Dermatol 2001 26 525 530 11678882
- [38]Ahn JH Lee Y Jeon C Identification of the genes differentially expressed in human dendritic cell subsets by cDNA subtraction and microarray analysis Blood 2002 100 1742 1754 12176896
Cited by
Sorted by citations
The single-cell transcriptional landscape of mammalian organogenesis
Cao, J., Spielmann, M., Qiu, X., Huang, X., Ibrahim, D. M., Hill, A. J., Zhang, F., Mundlos, S., Christiansen, L., Steemers, F. J., et al. (2019) · Nature · doi:10.1038/s41586-019-0969-x · Cited by 4,490 · see citing works
Higdon, C. W., Mitra, R. D., & Johnson, S. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067801 · Cited by 125 · see citing works
- Authors
- Tomihari, M., Hwang, S., Chung, J., Cruz Jr., P. D., & Ariizumi, K.
- Affiliations
- Dallas VA Medical Center (US)
- Corresponding author
- Ariizumi, Kiyoshi
- Venue
- Experimental Dermatology
- Publisher
- Wiley
- Published
- 2009-06-04
- Volume
- 18
- Issue
- 7
- Pages
- 586-595
- ISSN
- 0906-6705 (ISSN-L)
- 1600-0625
- PMC
- PMC2774115
- OpenAlex
- W2017712784
- Cited by
- 84
- References
- 2
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 2 · 2023: 6 · 2022: 2 · 2021: 9 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 9 · 2014: 5 · 2013: 6 · 2012: 2
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Dermatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service (A164927-01)
- National Institute of Allergy and Infectious Diseases (R01AI064927)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- GPNMB, melanosomes, RGD motif, integrin binding, melanocytes, keratinocytes, melanoma, UVA irradiation, alpha-melanocyte-stimulating hormone, interferon-gamma, TNF-α, cell surface expression, lysosomes, monoclonal antibodies
- MeSH terms
- Animals, Cell Adhesion, Cell Line, Cells, Cultured, Eye Proteins, Humans, Melanocytes, Melanoma, Membrane Glycoproteins, Oligopeptides, Skin Neoplasms, Ultraviolet Rays, Keratinocytes, Integrins, Melanosomes, Amino Acid Motifs, Cell Line, Tumor, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review