Plasmodium falciparum likely encodes the principal anion channel on infected human erythrocytes
Plasmodium falciparum likely encodes the principal anion channel on infected human erythrocytes
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DOI：
10.1182/blood-2004-05-2047
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发表时间：
2004-12-15
期刊：
影响因子：
20.3
通讯作者：
Desai, SA
中科院分区：
文献类型：
--
作者：
Alkhalil, A;Cohn, JV;Desai, SA
人类疟疾寄生虫恶性疟原虫的入侵与红细胞（RBC）膜通透性的显著但选择性的增加有关。我们以前确定了一个不寻常的电压依赖性离子通道，疟原虫表面阴离子通道（PSAC），这可能是这些增加。从那时起，出现了争议，是否有额外的寄生虫诱导的阴离子通道上的红细胞膜，这些通道是否寄生虫编码的蛋白质或内源性宿主蛋白质的修饰的结果。在这里，我们使用遗传上不同的寄生虫分离物和定量运输测量来研究这些问题。我们的研究表明，PSAC单独可以充分解释感染的红细胞对关键溶质的渗透性增加。两种不同的寄生虫分离株，生长在红细胞从一个单一的捐助者，表现出通道活动与可测量不同的电压依赖性门控，发现难以调和与简单的激活或修改的宿主蛋白。相反，通道门控的这种差异可以保守地解释为编码PSAC的寄生虫基因中的少量多态性。在完整的恶性疟原虫基因组中没有已知的真核细胞离子通道同源物，这表明了一种新的通道基因，并证实了PSAC作为抗疟药物开发的靶点。(C)2004年，美国血液学会。
Invasion by the human malaria parasite, Plasmodium falciparum, is associated with marked yet selective increases in red blood cell (RBC) membrane permeability. We previously identified an unusual voltage-dependent ion channel, the plasmodial surface anion channel (PSAC), which may account for these increases. Since then, controversy has arisen about whether there are additional parasite-induced anion channels on the RBC membrane and whether these channels are parasite-encoded proteins or the result of modifications of an endogenous host protein. Here, we used genetically divergent parasite isolates and quantitative transport measurements to examine these questions. Our studies indicate that PSAC alone can adequately account for the increased permeability of infected RBCs to key solutes. Two distinct parasite isolates, grown in RBCs from a single donor, exhibit channel activity with measurably different voltage-dependent gating, a finding difficult to reconcile with simple activation or modification of a host protein. Instead, this difference in channel gating can be conservatively explained by a small number of polymorphisms in a parasite gene that encodes PSAC. The absence of known eukaryotic ion channel homologues in the completed P falciparum genome suggests a novel channel gene, and substantiates PSAC as a target for antimalarial development. (C) 2004 by The American Society of Hematology.