Characterization of the chloroquine resistance transporter homologue in Toxoplasma gondii.

Characterization of the chloroquine resistance transporter homologue in Toxoplasma gondii.
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弓形虫中氯喹抗性转运蛋白同源物的表征。

DOI:
10.1128/ec.00027-14
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发表时间:
2014
期刊:
影响因子:
--
通讯作者:
vanDooren,GielG
vanDooren,GielG
中科院分区:
--
文献类型:
--
作者:
Warring,SallyD;Dou,Zhicheng;Carruthers,VernB;McFadden,GeoffreyI;vanDooren,GielG

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恶性疟原虫氯喹抗性转运蛋白(PfCRT)的突变赋予抗疟药氯喹的抗性。PfCRT定位于疟原虫的消化泡,氯喹作用的位点,在那里它通过将氯喹转运出消化泡来介导抗性。PfCRT属于被称为氯喹抗性转运蛋白家族的转运蛋白家族。CRT家族蛋白在顶复门、一些原生生物和植物中都有发现。尽管PfCRT在耐药性中的重要性,但对CRT蛋白的进化或天然功能知之甚少。顶复门寄生虫弓形虫含有一个CRT家族蛋白。我们证明了T.弓形虫CRT(TgCRT)与这些寄生虫中的空泡(VAC)隔室的标记物共定位。含有TgCRT的VAC是一种高度动态的细胞器,在寄生虫的细胞内和细胞外形式之间改变其形态和蛋白质组成。调节敲低TgCRT表达导致寄生虫适应性和VAC肿胀适度减少,表明TgCRT有助于寄生虫生长和VAC生理学。总之,我们的研究结果提供了CRT家族蛋白在顶复门寄生虫中的作用的新信息。
Mutations in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) protein confer resistance to the antimalarial drug chloroquine.PfCRT localizes to the parasite digestive vacuole, the site of chloroquine action, where it mediates resistance by transporting chloroquine out of the digestive vacuole.PfCRT belongs to a family of transporter proteins called the chloroquine resistance transporter family. CRT family proteins are found throughout the Apicomplexa, in some protists, and in plants. Despite the importance ofPfCRT in drug resistance, little is known about the evolution or native function of CRT proteins. The apicomplexan parasite Toxoplasma gondii contains one CRT family protein. We demonstrate that T. gondii CRT (TgCRT) colocalizes with markers for the vacuolar (VAC) compartment in these parasites. TheTgCRT-containing VAC is a highly dynamic organelle, changing its morphology and protein composition between intracellular and extracellular forms of the parasite. Regulated knockdown ofTgCRT expression resulted in modest reduction in parasite fitness and swelling of the VAC, indicating thatTgCRT contributes to parasite growth and VAC physiology. Together, our findings provide new information on the role of CRT family proteins in apicomplexan parasites.
DOI: 10.1007/978-1-4419-8414-2_4
发表时间: 2011
影响因子: --
作者:
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