Regulation of progenitor cell fusion by ABCB5 P-glycoprotein, a novel human ATP-binding cassette transporter
Regulation of progenitor cell fusion by ABCB5 P-glycoprotein, a novel human ATP-binding cassette transporter
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DOI：
10.1074/jbc.m308700200
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发表时间：
2003-11-21
影响因子：
4.8
通讯作者：
Frank, MH
中科院分区：
文献类型：
--
作者：
Frank, NY;Pendse, SS;Frank, MH
涉及祖细胞的细胞融合是一种新认识的现象，被认为有助于组织分化。控制细胞融合的分子机制尚不清楚。 P-糖蛋白和相关的 ATP 结合盒转运蛋白由祖细胞表达，但它们在这些细胞类型中的生理作用尚未确定。在这里，我们克隆了 ABCB5，一种罗丹明外排转运蛋白，也是人类 P-糖蛋白家族的新成员，它标记了人类表皮黑素细胞中表达 CD133 的祖细胞，并作为膜电位的调节剂决定了该亚群进行细胞融合的倾向。我们的研究结果表明，多倍体 ABCB5 (+) 细胞是通过细胞融合产生的，并且 ABCB5 P-糖蛋白阻断特别增强了这一过程。值得注意的是，多核细胞杂交产生了单核后代，证明融合有助于培养物的生长和分化。因此，我们的研究结果定义了涉及祖细胞的细胞融合的分子机制，并表明融合和由此产生的生长和分化不仅仅是自发事件，而且是由ABCB5 P-糖蛋白调节的现象。
Cell fusion involving progenitor cells is a newly recognized phenomenon thought to contribute to tissue differentiation. The molecular mechanisms governing cell fusion are unknown. P- glycoprotein and related ATP- binding cassette transporters are expressed by progenitor cells, but their physiological role in these cell types has not been defined. Here, we have cloned ABCB5, a rhodamine efflux transporter and novel member of the human P- glycoprotein family, which marks CD133- expressing progenitor cells among human epidermal melanocytes and determines as a regulator of membrane potential the propensity of this subpopulation to undergo cell fusion. Our findings show that polyploid ABCB5 (+) cells are generated by cell fusion and that this process is specifically enhanced by ABCB5 P-glycoprotein blockade. Remarkably, multinucleated cell hybrids gave rise to mononucleated progeny, demonstrating that fusion contributes to culture growth and differentiation. Thus, our findings define a molecular mechanism for cell fusion involving progenitor cells and show that fusion and resultant growth and differentiation are not merely spontaneous events, but phenomena regulated by ABCB5 P- glycoprotein.