The binding of the circumsporozoite protein to cell surface heparan sulfate proteoglycans is required for Plasmodium sporozoite attachment to target cells
The binding of the circumsporozoite protein to cell surface heparan sulfate proteoglycans is required for Plasmodium sporozoite attachment to target cells
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DOI：
10.1074/jbc.m104038200
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发表时间：
2001-07-20
影响因子：
4.8
通讯作者：
Sinnis, P
中科院分区：
文献类型：
--
作者：
Pinzon-Ortiz, C;Friedman, J;Sinnis, P
疟疾孢子子的主要表面蛋白环孢子子蛋白与肝细胞表面的硫酸肝素蛋白聚糖结合。有人提出，这种结合事件是孢子虫被感染的按蚊注射到皮肤后迅速和特异性定位到肝脏的原因。先前在静态条件下进行的体外研究未能证明硫酸肝素蛋白聚糖在孢子子侵入细胞过程中的重要作用。我们在更动态的条件下进行了孢子体附着和侵袭实验，发现肝素存在时孢子体对细胞的附着显著减少。与肝素对附着的影响相反，肝素似乎对孢子体对细胞的侵袭没有影响。当取代肝素被用作孢子体附着的竞争性抑制剂时，我们发现在Nand o位置的糖胺聚糖链的磺化对于孢子体与细胞的粘附是重要的。我们得出结论，环孢子子蛋白与肝硫酸肝素蛋白聚糖的结合可能在孢子子在肝脏中的附着过程中起作用，并且这种粘附事件取决于蛋白聚糖的硫酸化糖胺聚糖链。
The major surface protein of malaria sporozoites, the circumsporozoite protein, binds to heparan sulfate proteoglycans on the surface of hepatocytes. It has been proposed that this binding event is responsible for the rapid and specific localization of sporozoites to the liver after their injection into the skin by an infected anopheline mosquito. Previous in vitro studies performed under static conditions have failed to demonstrate a significant role for heparan sulfate proteoglycans during sporozoite invasion of cells. We performed sporozoite attachment and invasion assays under more dynamic conditions and found a dramatic decrease in sporozoite attachment to cells in the presence of heparin, In contrast to its effect on attachment, heparin does not appear to have an effect on sporozoite invasion of cells. When substituted heparins were used as competitive inhibitors of sporozoite attachment, we found that sulfation of the glycosaminoglycan chains at both the Nand O-positions was important for sporozoite adhesion to cells. We conclude that the binding of the circumsporozoite protein to hepatic heparan sulfate proteoglycans is likely to function during sporozoite attachment in the liver and that this adhesion event depends on the sulfated glycosaminoglycan chains of the proteoglycans.