Identification of basal complex protein that is essential for maturation of transmission-stage malaria parasites.
Identification of basal complex protein that is essential for maturation of transmission-stage malaria parasites.
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DOI：
10.1073/pnas.2204167119
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发表时间：
2022-08-23
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
疟疾是由疟原虫寄生虫引起的，对公共卫生造成重大负担。恶性疟原虫是导致最严重形式的疟疾的寄生虫，在配子体阶段的发育期间经历大量变态，这是疟疾寄生虫传播所必需的。我们发现了一种新的蛋白质PfBLEB，它在传播阶段的成熟过程中协调寄生虫的重塑，并且是发育中的配子体存活所必需的。总体而言，我们发现PfBLEB是重要的形态发生和扩展的独特的寄生虫细胞骨架在恶性疟原虫配子体，因为它们成熟。我们的发现揭示了寄生虫细胞生物学，并为开发阻断疟疾传播的药物提供了潜在的分子靶点。疟疾仍然是全球发病率和死亡率的一个驱动因素。为了产生新的抗疟药，必须阐明恶性疟原虫的基本细胞生物学，恶性疟原虫是导致最致命疟疾病例的寄生虫。被称为内膜复合物（IMC）的膜状和蛋白质支架在形态变化期间支持寄生虫，包括无性复制期间的子细胞分割和传播阶段配子体的形成。基底复合体在分割期间为IMC的边缘划线，并且可能促进IMC扩张。然而，目前还不清楚是什么驱动IMC在配子体发生过程中的扩张。我们描述了一个基础的复杂蛋白质，PfBLEB，我们发现是必不可少的配子体发生的发现。缺乏PfBLEB的寄生虫在IMC扩增中存在缺陷，并且不能形成成熟的配子体。这篇文章展示了一个基本的复杂蛋白质的作用以外的无性分裂，重要的是，突出了一个潜在的分子靶点消融疟疾传播。
Malaria, which is caused by Plasmodium parasites, poses a significant public health burden. P. falciparum, the parasite responsible for the most severe forms of malaria, undergoes substantial metamorphosis during the development of gametocyte stages, which are required for the transmission of malaria parasites. We discovered a novel protein, PfBLEB, that orchestrates parasite remodeling during the maturation of transmission stages and is required for the survival of developing gametocytes. Overall, we find that PfBLEB is important for the morphogenesis and expansion of the unique parasite cytoskeleton in P. falciparum gametocytes as they mature. Our findings reveal parasite cell biology and shed light on potential molecular targets for the development of drugs that could block malaria transmission. Malaria remains a global driver of morbidity and mortality. To generate new antimalarials, one must elucidate the fundamental cell biology of Plasmodium falciparum, the parasite responsible for the deadliest cases of malaria. A membranous and proteinaceous scaffold called the inner membrane complex (IMC) supports the parasite during morphological changes, including segmentation of daughter cells during asexual replication and formation of transmission-stage gametocytes. The basal complex lines the edge of the IMC during segmentation and likely facilitates IMC expansion. It is unknown, however, what drives IMC expansion during gametocytogenesis. We describe the discovery of a basal complex protein, PfBLEB, which we find to be essential for gametocytogenesis. Parasites lacking PfBLEB harbor defects in IMC expansion and are unable to form mature gametocytes. This article demonstrates a role for a basal complex protein outside of asexual division, and, importantly, highlights a potential molecular target for the ablation of malaria transmission.
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DOI：
10.1016/s0022-5320(69)80010-9
发表时间：
1969-01-01
期刊：
JOURNAL OF ULTRASTRUCTURE RESEARCH
影响因子：
--
作者：
AIKAWA, M;HUFF, CG;SPRINZ, H
通讯作者：
SPRINZ, H
影响因子：
4
作者：
Dearnley, Megan K.;Yeoman, Jeffrey A.;Dixon, Matthew W. A.
通讯作者：
Dixon, Matthew W. A.
影响因子：
16.6
作者：
Ganesan, Suresh M.;Falla, Alejandra;Niles, Jacquin C.
通讯作者：
Niles, Jacquin C.
影响因子：
3.4
作者：
Engelberg K;Ivey FD;Lin A;Kono M;Lorestani A;Faugno-Fusci D;Gilberger TW;White M;Gubbels MJ
通讯作者：
Gubbels MJ
影响因子：
--
作者：
Ferguson, David J. P.;Sahoo, Nivedita;Gubbels, Marc-Jan
通讯作者：
Gubbels, Marc-Jan