Functional Analysis of the Exported Type IV HSP40 Protein PfGECO in Plasmodium falciparum Gametocytes
Functional Analysis of the Exported Type IV HSP40 Protein PfGECO in Plasmodium falciparum Gametocytes
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DOI：
10.1128/ec.05155-11
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发表时间：
2011-11-01
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影响因子：
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通讯作者：
Williamson, Kim C.
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作者：
Morahan, Belinda J.;Strobel, Carolyn;Williamson, Kim C.
在恶性疟原虫感染过程中，宿主红细胞(RBC)重塑是疟原虫生存所必需的。这种修饰是通过将寄生虫蛋白输出到红细胞中来介导的，这种蛋白质改变了红细胞膜的结构，使细胞能够黏附。这可能是因为一些出口蛋白也对宿主的防御反应起到了保护作用。这对于导致疟疾传播的生命周期中的配子体阶段可能特别重要，因为配子体在12天的成熟过程中经历了五个形态阶段(I到V)时，仍然与血液接触。利用微阵列分析，我们鉴定了几个在配子发生早期差异表达的具有编码的分泌或输出序列的基因。其中，PfGECO编码一种预测的IV型热休克蛋白40(Hsp40)，我们发现它在配子体I到IV阶段表达，并输出到RBC细胞质。传统上，热休克蛋白是在应激条件下诱导的，以维持体内平衡，但PfGECO的表达在热休克时不会增加，这表明了另一种功能。靶向阻断PfGECO基因表明该基因在体外配子体发生中不是必需的，定量逆转录聚合酶链式反应(RT-PCR)显示其他IV型Hsp40基因没有补偿性表达。尽管恶性疟原虫Hsp40成员参与了蛋白质向红细胞表面的运输，但PfGECO的去除并不影响其他出口配子体蛋白的靶向。这项工作扩大了已知的配子体输出蛋白的谱系，包括IV型Hsp40，PfGECO。
During Plasmodium falciparum infection, host red blood cell (RBC) remodeling is required for the parasite's survival. Such modifications are mediated by the export of parasite proteins into the RBC that alter the architecture of the RBC membrane and enable cytoadherence. It is probable that some exported proteins also play a protective role against the host defense response. This may be of particular importance for the gametocyte stage of the life cycle that is responsible for malaria transmission, since the gametocyte remains in contact with blood as it proceeds through five morphological stages (I to V) during its 12-day maturation. Using microarray analysis, we identified several genes with encoded secretory or export sequences that were differentially expressed during early gametocytogenesis. One of these, PfGECO, encodes a predicted type IV heat shock protein 40 (HSP40) that we show is expressed in gametocyte stages I to IV and is exported to the RBC cytoplasm. HSPs are traditionally induced under stressful conditions to maintain homeostasis, but PfGECO expression was not increased upon heat shock, suggesting an alternate function. Targeted disruption of PfGECO indicated that the gene is not essential for gametocytogenesis in vitro, and quantitative reverse transcriptase PCR (RT-PCR) showed that there was no compensatory expression of the other type IV HSP40 genes. Although P. falciparum HSP40 members are implicated in the trafficking of proteins to the RBC surface, removal of PfGECO did not affect the targeting of other exported gametocyte proteins. This work has expanded the repertoire of known gametocyte-exported proteins to include a type IV HSP40, PfGECO.