Plasmodium knowlesi Skeleton-Binding Protein 1 Localizes to the 'Sinton and Mulligan' Stipplings in the Cytoplasm of Monkey and Human Erythrocytes.

Plasmodium knowlesi Skeleton-Binding Protein 1 Localizes to the 'Sinton and Mulligan' Stipplings in the Cytoplasm of Monkey and Human Erythrocytes.
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DOI:
10.1371/journal.pone.0164272
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Kaneko O
Kaneko O
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lucky AB;Sakaguchi M;Katakai Y;Kawai S;Yahata K;Templeton TJ;Kaneko O

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疟疾寄生虫,疟原虫,出口蛋白质产品感染的红细胞,引入必要的修改建立营养收购和表面展示主机相互作用配体。红细胞重塑影响寄生虫毒力和疾病病理学,并且对人类疟疾寄生虫恶性疟原虫有充分记载,但对其他疟原虫物种的描述较少。对于恶性疟原虫,输出的蛋白质结合蛋白1(PfSBP 1)参与红细胞表面配体的运输,并定位于感染的红细胞内的膜结构,称为毛雷尔裂。在这项研究中,我们通过BLAST分析和保守基因同线性分析了疟原虫属中的SBP1直系同源物,这也是de Niz等人最近描述的。为了评估SBP1直系同源物的定位,我们利用人畜共患疟疾寄生虫,诺氏疟原虫。表达表位标记的重组PkSBP1的转基因诺氏疟原虫的免疫荧光测定显示,在感染猴或人红细胞后,出现了令人想起Maurer's clefts的点状染色模式。重组PkSBP 1阳性斑点与Giemsa染色的结构共定位,称为“辛顿和Mulligan”点画。免疫电子显微镜还显示,重组PkSBP1定位内或上的膜结构类似于毛雷尔的裂缝。在恶性疟原虫感染的红细胞中表达的重组PkSBP 1与PfSBP 1共定位于Maurer's裂隙,表明类似的运输模式。诺氏疟原虫2TM蛋白家族的一个成员也在感染的猴红细胞中表达并定位于膜结构。这些结果表明,诺氏疟原虫的运输机制和诱导的红细胞结构在感染猴和人红细胞后是相似的,并且与恶性疟原虫是保守的。
The malaria parasite, Plasmodium, exports protein products to the infected erythrocyte to introduce modifications necessary for the establishment of nutrient acquisition and surface display of host interaction ligands. Erythrocyte remodeling impacts parasite virulence and disease pathology and is well documented for the human malaria parasite Plasmodium falciparum, but has been less described for other Plasmodium species. For P. falciparum, the exported protein skeleton-binding protein 1 (PfSBP1) is involved in the trafficking of erythrocyte surface ligands and localized to membranous structures within the infected erythrocyte, termed Maurer's clefts. In this study, we analyzed SBP1 orthologs across the Plasmodium genus by BLAST analysis and conserved gene synteny, which were also recently described by de Niz et al. (2016). To evaluate the localization of an SBP1 ortholog, we utilized the zoonotic malaria parasite, Plasmodium knowlesi. Immunofluorescence assay of transgenic P. knowlesi parasites expressing epitope-tagged recombinant PkSBP1 revealed a punctate staining pattern reminiscent of Maurer's clefts, following infection of either monkey or human erythrocytes. The recombinant PkSBP1-positive puncta co-localized with Giemsa-stained structures, known as ‘Sinton and Mulligan’ stipplings. Immunoelectron microscopy also showed that recombinant PkSBP1 localizes within or on the membranous structures akin to the Maurer's clefts. The recombinant PkSBP1 expressed in P. falciparum-infected erythrocytes co-localized with PfSBP1 at the Maurer's clefts, indicating an analogous trafficking pattern. A member of the P. knowlesi 2TM protein family was also expressed and localized to membranous structures in infected monkey erythrocytes. These results suggest that the trafficking machinery and induced erythrocyte cellular structures of P. knowlesi are similar following infection of both monkey and human erythrocytes, and are conserved with P. falciparum.
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