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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Dual stage synthesis and crucial role of cytoadherence-linked asexual gene 9 in the surface expression of malaria parasite var proteins
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Dual stage synthesis and crucial role of cytoadherence-linked asexual gene 9 in the surface expression of malaria parasite var proteins

机译：细胞粘附相关无性基因9的双重合成及其在疟疾寄生虫var蛋白表面表达中的关键作用

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摘要

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family members mediate the adherence of parasite-infected red blood cells (IRBCs) to various host receptors. A previous study has shown that the parasite protein, cytoadherence-linked asexual gene 9 (CLAG9), is also essential for IRBC adherence. However, how CLAG9 influences this process remains unknown. In this study, we show that CLAG9 interacts with VAR2CSA, a PfEMPI that mediates IRBC adherence to chondroitin 4-sulfate in the placenta. Importantly, our results show that the adherent parasites synthesize CLAG9 at two stages-the early ring and late trophozoite stages. Localization studies revealed that a substantial level of CLAG9 is located mainly at or in close proximity of the IRBC membrane in association with VAR2CSA. Upon treatment of IRBCs with trypsin, a significant amount of CLAG9 (≈150 kDa) was converted into ≈142-kDa polypeptide. Together these data demonstrate that a considerable amount of CLAG9 is embedded in the IRBC membrane such that at least a portion of the polypeptide at either N or C terminus is exposed on the cell surface. In parasites lacking CLAG9, VAR2CSA failed to express on the IRBC surface and was located within the parasite. Based on these findings, we propose that CLAG9 plays a critical role in the trafficking of PfEMP1s onto the IRBC surface. These results have important implications for the development of therapeutics for cerebral, placental, and other cytoadherence-associated malaria illnesses.
机译：恶性疟原虫红细胞膜蛋白1（PfEMP1）家庭成员介导寄生虫感染的红细胞（IRBCs）粘附到各种宿主受体。先前的研究表明，寄生虫蛋白（与细胞粘附相关的无性基因9（CLAG9））对于IRBC粘附也是必不可少的。但是，CLAG9如何影响此过程仍然未知。在这项研究中，我们表明CLAG9与VAR2CSA相互作用，VAR2CSA是一种PfEMPI，可介导IRBC粘附于胎盘中的4-硫酸软骨素。重要的是，我们的结果表明粘附的寄生虫在环的早期和滋养体的两个阶段合成了CLAG9。本地化研究表明，大量的CLAG9主要位于与VAR2CSA结合的IRBC膜上或附近。用胰蛋白酶处理IRBC后，大量的CLAG9（≈150kDa）被转化为≈142-kDa多肽。这些数据一起证明，大量的CLAG9嵌入IRBC膜中，从而至少一部分多肽在N或C末端暴露在细胞表面。在缺少CLAG9的寄生虫中，VAR2CSA无法在IRBC表面表达，并且位于该寄生虫内。基于这些发现，我们建议CLAG9在将PfEMP1s转运到IRBC表面上起关键作用。这些结果对脑，胎盘和其他与细胞粘附相关的疟疾的治疗方法的开发具有重要意义。

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    Suchi Goel; Manojkumar Valiyaveettil; Rajeshwara N. Achur; Atul Goyal; Denise Mattei; Ali Salanti; Katharine R. Trenholme; Donald L. Gardiner; D. Channe Gowda;

  • 作者单位

    Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033;

    rnDepartment of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033;

    rnDepartment of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033 Department of Biochemistry, Kuvempu University, Karnataka 577451, India;

    rnDepartment of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033;

    rnBiology of Host-Parasite Interactions Unit, Centre National de la Recherche Scientifique Unite de Recherche Associee 2581, Institut Pasteur, F-75724 Paris Cedex 15, France;

    rnInstitute of International Health, Immunology, and Microbiology, 2100 Copenhagen, Denmark;

    rnMalaria Biology Laboratory, Queensland Institute of Medical Research, Herston, Queensland 4006, Australia;

    rnMalaria Biology Laboratory, Queensland Institute of Medical Research, Herston, Queensland 4006, Australia;

    rnDepartment of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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  • 关键词

    plasmodium falciparum; erythrocyte membrane protein 1; VAR2CSA; trafficking; localization;

    机译：恶性疟原虫红细胞膜蛋白1;VAR2CSA;贩运;本土化;

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