The upstream sequence segment of the C-terminal cysteine-rich domain is required for microneme trafficking of Plasmodium falciparum erythrocyte binding antigen 175
The upstream sequence segment of the C-terminal cysteine-rich domain is required for microneme trafficking of Plasmodium falciparum erythrocyte binding antigen 175
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DOI：
10.1016/j.parint.2012.12.002
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发表时间：
2013-04-01
影响因子：
1.9
通讯作者：
Kaneko, Osamu
中科院分区：
文献类型：
--
作者：
Sakura, Takaya;Yahata, Kazuhide;Kaneko, Osamu
红细胞侵入是疟原虫（疟疾的病原体）在其宿主中存活的关键步骤，并且疟原虫红细胞结合样（EBL）蛋白对宿主细胞受体的识别起着重要作用。虽然EBL亚细胞定位显示出与啮齿动物疟疾模型中的寄生虫毒力密切相关，但EBL向微线体的贩运，侵入性寄生虫中的分泌细胞器尚未完全了解。在这项研究中，我们评估了恶性疟原虫EBL（EBA-175）的缺失和氨基酸替换的影响，使用转基因恶性疟原虫株系表达修饰的EBA-175。我们发现，除了信号肽和富含半胱氨酸的区域（区域6）的胞质尾，一个以前未被识别的序列片段在区域5所需的正确的微线贩运EBA-175。替换精氨酸或苯丙氨酸残基在这段改变微线贩运，表明序列本身包含的关键信息。基于这些发现，我们建议，区域5中的序列片段也需要识别EBA-175的贩运机制，以指导这种蛋白质的微线。我们的研究结果提供了关键信息，以澄清一个尚未确定的EBA-175贩运机制。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Erythrocyte invasion is a critical step for survival of Plasmodium parasites, the causative agents of malaria, in their host and recognition of the host cell receptors by Plasmodium erythrocyte-binding-like (EBL) proteins plays an important role. Although EBL subcellular localization was shown to be closely linked to parasite virulence in the rodent model of malaria, the trafficking of EBL to micronemes, the secretory organelle in the invasive parasite is not fully understood. In this study, we assessed the impact of the deletion and amino acid replacement of Plasmodium falciparum EBL (EBA-175) using transgenic P. falciparum lines expressing modified EBA-175. We found that, in addition to a signal peptide and a cysteine rich region (region 6) to the cytoplasmic tail, a previously unrecognized sequence segment in region 5 was required for correct microneme trafficking of EBA-175. Replacement of Arg or Phe residues in this segment altered microneme trafficking, suggesting that the sequence itself contained critical information. Based on these findings, we propose that the sequence segment in region 5 is also required for the recognition of EBA-175 by the trafficking machinery to direct this protein to the microneme. Our results provide key information to clarify an as yet unidentified EBA-175 trafficking mechanism. (C) 2012 Elsevier Ireland Ltd. All rights reserved.