Essential function of alveolin PfIMC1g in the Plasmodium falciparum asexual blood stage.
Essential function of alveolin PfIMC1g in the Plasmodium falciparum asexual blood stage.
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DOI：
10.1128/mbio.01507-23
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发表时间：
2023-10-31
期刊：
影响因子：
6.4
通讯作者：
Kumar, Nirbhay
中科院分区：
文献类型：
--
作者：
Cepeda Diaz, Ana Karla;Rudlaff, Rachel M.;Farringer, Madeline;Dvorin, Jeffrey D.;Kumar, Nirbhay
疟原虫的细胞骨架对于疟原虫的复制、运动和感染性是必不可少的。恶性疟原虫利用称为肺泡蛋白的细胞骨架蛋白家族来满足这些不同的需求。然而，个体肺泡蛋白在疟原虫血液阶段中的功能作用仍未被探索。在这里，我们证明了alveolin PfIMC 1g（PF3D7_0525800）是恶性疟原虫无性复制所必需的。与在蚊子阶段研究的肺泡蛋白不同，PfIMC 1g在决定细胞形状方面不起重要作用。PfIMC1g缺陷的寄生虫在分割过程中仅表现出轻微的缺陷，大多数裂殖子通过超分辨率荧光显微镜、超微结构扩增显微镜和电子显微镜与野生型无法区分。在目前的研究中，我们证明，PfIMC 1g的情况下导致寄生虫死亡后不久裂殖子内化到红细胞（RBC）。PfIMC1g缺陷型寄生虫排出并进入新的RBC，但未能发育成环并死亡。我们假设PfIMC 1g的主要作用是保持结构完整性，保护寄生虫在内化过程中免受损害。沿着PfIMC 1g对裂殖子细胞形状的可分性，我们报告了关于疟原虫肺泡蛋白的结构的新发现，包括PfIMC 1e和1f在基底复合物的定位。恶性疟原虫寄生虫感染是最严重的人类疟疾形式。寄生虫的无性血液阶段发生在人类红细胞内，是疟疾症状的原因，也是大多数抗疟药物的目标。疟原虫属依靠其高度分散的细胞骨架结构来支撑其细胞分裂，维持入侵的机械应力，并在人类血液和蚊子中存活。我们调查的功能，一类分歧的中间趋化样蛋白称为肺泡蛋白在临床上重要的血液阶段。由于基因敲除的多效性和肺泡蛋白之间的冗余，单个肺泡蛋白在疟原虫中的功能作用仍然知之甚少。我们评估的定位和必要性的四个无性阶段的肺泡，发现PfIMC 1g和PfIMC 1c是必不可少的。此外，我们证明了PfIMC 1g对寄生虫入侵后的生存至关重要。
The cytoskeleton of Plasmodium parasites is essential for replication, motility, and infectivity. Plasmodium falciparum leverages a family of cytoskeletal proteins known as alveolins to meet these diverse needs. The functional role of individual alveolins in Plasmodium blood stages, however, remains unexplored. Here, we demonstrate that the alveolin PfIMC1g (PF3D7_0525800) is essential for P. falciparum asexual replication. Unlike alveolins studied in mosquito stages, PfIMC1g does not play an important role in determining cell shape. PfIMC1g-deficient parasites exhibit only minor defects during segmentation, with most merozoites being indistinguishable from wild type by super-resolution fluorescence microscopy, ultrastructure expansion microscopy, and electron microscopy. In the current study, we demonstrate that the absence of PfIMC1g leads to parasite death shortly after merozoite internalization into red blood cells (RBCs). PfIMC1g-deficient parasites egress and enter new RBCs but fail to develop into rings and die. We hypothesize that the primary role of PfIMC1g is to maintain structural integrity, protecting parasites from incurring damage during the process of internalization. Along with the dispensability of PfIMC1g for merozoite cell shape, we report new findings about the architecture of Plasmodium alveolins including the localization of PfIMC1e and 1f to the basal complex. Infection by the Plasmodium falciparum parasite is responsible for the most severe form of human malaria. The asexual blood stage of the parasite, which occurs inside human red blood cells, is responsible for the symptoms of malaria and is the target of most antimalarial drugs. Plasmodium spp. rely on their highly divergent cytoskeletal structures to scaffold their cell division, sustain the mechanical stress of invasion, and survive in both the human bloodstream and the mosquito. We investigate the function of a class of divergent intermediate filament-like proteins called alveolins in the clinically important blood stage. The functional role of individual alveolins in Plasmodium remains poorly understood due to pleiotropic effects of gene knockouts and redundancy among alveolins. We evaluate the localization and essentiality of the four asexual-stage alveolins and find that PfIMC1g and PfIMC1c are essential. Furthermore, we demonstrate that PfIMC1g is critical for survival of the parasite post-invasion.
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影响因子：
9.8
作者：
Bozdech, Zbynek;Llinas, Manuel;Pulliam, Brian Lee;Wong, Edith D;Zhu, Jingchun;DeRisi, Joseph L
通讯作者：
DeRisi, Joseph L
影响因子：
9.8
作者：
Bertiaux E;Balestra AC;Bournonville L;Louvel V;Maco B;Soldati-Favre D;Brochet M;Guichard P;Hamel V
通讯作者：
Hamel V
影响因子：
6.7
作者：
Collins CR;Hackett F;Strath M;Penzo M;Withers-Martinez C;Baker DA;Blackman MJ
通讯作者：
Blackman MJ
影响因子：
16.6
作者：
Gruering, Christof;Heiber, Arlett;Spielmann, Tobias
通讯作者：
Spielmann, Tobias
DOI：
10.1073/pnas.1619441114
发表时间：
2017-03-28
影响因子：
11.1
作者：
Hale, Victoria L.;Watermeyer, Jean M.;Saibil, Helen R.
通讯作者：
Saibil, Helen R.