Disruption of a Plasmodium falciparum gene linked to male sexual development causes early arrest in gametocytogenesis
Disruption of a Plasmodium falciparum gene linked to male sexual development causes early arrest in gametocytogenesis
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DOI：
10.1073/pnas.0501858102
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发表时间：
2005-11-15
影响因子：
11.1
通讯作者：
Su, XZ
中科院分区：
文献类型：
--
作者：
Furuya, T;Mu, JB;Su, XZ
恶性疟原虫Dd 2寄生虫中的雄性配子体缺陷先前通过观察发现，Dd 2 x HB 3遗传杂交中的所有子代克隆都是Dd 2雌性和HB 3雄性配子之间受精事件的结果。随后将与Dd 2缺陷相关的决定子映射到12号染色体上的800 kb片段。在这里，我们报告进一步映射到一个82 kb的区域和一个候选基因，P. faiciparum雄性发育基因1（pfmdv-1），这是在较低的水平表达的Dd 2相比，野生型正常的雄性配子体生产的祖先W2的决定因素。Pfmdv-1蛋白是性阶段特异性的，位于配子体质膜、寄生虫空泡膜和红细胞内裂缝样结构的膜上。pfmdv-1的破坏导致成熟配子体，特别是功能性雄配子体的急剧减少，大多数性定向寄生虫在第1阶段发育停滞。pfmdv-1基因敲除的寄生虫表现出紊乱的膜结构，特别是可能来源于变形裂缝样结构的多膜囊泡/管。敲除寄生虫的Moscovirus感染性也大大降低，但没有完全丧失。结果表明pfmdv-1在配子体膜的形成和完整性中起关键作用。
A male gametocyte defect in the Plasmodium falciparum Dd2 parasite was previously discovered through the observation that all progeny clones in a Dd2 x HB3 genetic cross were the result of fertilization events between Dd2 female and HB3 male gametes. A determinant linked to the defect in Dd2 was subsequently mapped to an 800-kb segment on chromosome 12. Here, we report further mapping of the determinant to an 82-kb region and the identification of a candidate gene, P. faiciparum male development gene 1 (pfmdv-1), that is expressed at a lower level in Dd2 compared with the wild-type normal male gametocyte-producing ancestor W2. Pfmdv-1 protein is sexual-stage specific and is located on the gametocyte plasma membrane, parasitophorous vacuole membrane, and the membranes of cleft-like structures within the erythrocyte. Disruption of pfmdv-1 results in a dramatic reduction in mature gametocytes, especially functional male gametocytes, with the majority of sexually committed parasites developmentally arrested at stage 1. The pfmdv-1-knockout parasites show disturbed membrane structures, particularly multimembrane vesicles/tubes that likely derive from deformed cleft-like structures. Mosquito infectivity of the knockout parasites was also greatly reduced but not completely lost. The results suggest that pfmdv-1 plays a key role in gametocyte membrane formation and integrity.