A Novel Function of Heparan Sulfate in the Regulation of Cell-Cell Fusion
A Novel Function of Heparan Sulfate in the Regulation of Cell-Cell Fusion
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DOI：
10.1074/jbc.m109.037960
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发表时间：
2009-10-23
影响因子：
4.8
通讯作者：
Shukla, Deepak
中科院分区：
文献类型：
--
作者：
O'Donnell, Christopher D.;Shukla, Deepak
尽管细胞与细胞融合在真核生物的发育和生理学中做出了重要贡献，但人们对调节这一过程的机制知之甚少。我们的研究表明，细胞表面和细胞外基质表达的糖胺聚糖，更具体地说是硫酸乙酰肝素 (HS)，可能充当细胞-细胞融合的负调节剂。使用 1 型单纯疱疹病毒作为增强细胞间融合的工具，我们证明细胞表面 HS 表达的缺失会导致细胞间融合的显着增强。当使用其他病毒或聚乙二醇作为融合增强剂时，观察到相同的现象。 HS 生物合成缺陷的细胞表现出两种 Rho GTP 酶（RhoA 和 Cdc42）活性增加，这两种酶都显示出活性增加与细胞间融合增强之间的相关性。这可以解释为什么 HS 缺陷细胞表现出显着增强的细胞间融合，并表明 HS 可以通过微调 RhoA 和 Cdc42 活性来调节融合。
Despite the important contribution of cell-cell fusion in the development and physiology of eukaryotes, little is known about the mechanisms that regulate this process. Our study shows that glycosaminoglycans and more specifically heparan sulfate (HS) expressed on the cell surface and extracellular matrix may act as negative regulator of cell-cell fusion. Using herpes simplex virus type-1 as a tool to enhance cell-cell fusion, we demonstrate that the absence of HS expression on the cell surface results in a significant increase in cell-cell fusion. An identical phenomenon was observed when other viruses or polyethylene glycol was used as fusion enhancer. Cells deficient in HS biosynthesis showed increased activity of two Rho GTPases, RhoA and Cdc42, both of which showed a correlation between increased activity and increased cell-cell fusion. This could serve as a possible explanation as to why HS-deficient cells showed significantly enhanced cell-cell fusion and suggests that HS could regulate fusion via fine tuning of RhoA and Cdc42 activities.