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

Gpnmb is a melanosome-associated glycoprotein that contributes to melanocyte/keratinocyte adhesion in a RGD-dependent fashion.
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DOI:
10.1111/j.1600-0625.2008.00830.x
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发表时间:
2009-07
影响因子:
3.6
通讯作者:
Ariizumi K
Ariizumi K
中科院分区:
医学2区
文献类型:
--
作者:
Tomihari M;Hwang SH;Chung JS;Cruz PD Jr;Ariizumi K

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gpnmb是一种糖基化的跨膜蛋白,与小鼠青光眼和人类黑色素瘤的发生有关。它与黑素体蛋白Pmel-17共享显著的氨基酸序列同源性。其胞外结构域含有用于结合整联蛋白的RGD基序,其胞内结构域具有推定的内体和/或黑素体分选基序。这些特征使我们确定Gpnmb与黑素体相关并参与细胞粘附。我们发现,人Gpnmb组成型表达的黑色素瘤细胞系,原代培养的黑素细胞,和表皮黑素细胞原位,其中大部分被发现细胞内的黑素体和溶酶体中的程度较低。我们新开发的单克隆抗体揭示了这些色素细胞上Gpnmb的表面表达,尽管程度低于细胞内部分。UVA(而非UVB)照射和α-MSH(而非β-MSH)可上调Gpnmb的表达; IFN-γ和TNF-α可显著增加其在黑素细胞(而非黑色素瘤细胞)表面的表达。PAM 212角质形成细胞以RGD依赖性方式粘附于固定化的Gpnmb。这些结果表明,Gpnmb是一种黑素体相关糖蛋白,有助于黑素细胞与角质形成细胞的粘附。
Gpnmb is a glycosylated transmembrane protein implicated in 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-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 adhesion of melanocytes with keratinocytes.
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