A developmental defect in Plasmodium falciparum male gametogenesis.
A developmental defect in Plasmodium falciparum male gametogenesis.
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DOI：
10.1083/jcb.135.1.269
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发表时间：
1996-10
期刊：
影响因子：
--
通讯作者：
Wellems TE
中科院分区：
文献类型：
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作者：
Guinet F;Dvorak JA;Fujioka H;Keister DB;Muratova O;Kaslow DC;Aikawa M;Vaidya AB;Wellems TE
疟原虫的无性繁殖种群，包括那些来自克隆系的疟原虫，产生雄性和雌性配子，通过蚊子完成疟疾的生命周期。这些有性形式的产生始于脊椎动物宿主血液中单倍体无性阶段寄生虫的配子体的诱导。支配有性形式的分化和发育的分子过程在很大程度上是未知的。在这里，我们描述了一个缺陷，影响发展的主管男性配子母细胞从突变克隆的恶性疟原虫（Dd 2）。Dd 2克隆与其衍生的前体克隆（W2'82）的比较表明，缺陷是在体外无性阶段的长期培养期间产生的突变。光学和电子显微镜图像以及用雄性特异性抗α-微管蛋白II抗体进行的间接免疫荧光测定表明，相对于W2'82，Dd 2克隆在配子母细胞水平上对雄性发育造成了全面破坏，成熟雄性配子母细胞的比例至少降低了70-90%。异常配子体形式的高患病率，经常包含多个和异常大的空泡，与缺陷有关。成熟雄性配子母细胞产量的减少可能反映了配子母细胞在雄性发育过程中存在的问题，或成熟过程中有活力的雄性配子母细胞的逐渐消耗。这种缺陷在遗传上与几乎完全没有雄性配子产生和对蚊子的感染性有关。这是第一个性别特异性发育突变的确定和特点的疟原虫。
Asexually replicating populations of Plasmodium parasites, including those from cloned lines, generate both male and female gametes to complete the malaria life cycle through the mosquito. The generation of these sexual forms begins with the induction of gametocytes from haploid asexual stage parasites in the blood of the vertebrate host. The molecular processes that govern the differentiation and development of the sexual forms are largely unknown. Here we describe a defect that affects the development of competent male gametocytes from a mutant clone of P. falciparum (Dd2). Comparison of the Dd2 clone to the predecessor clone from which it was derived (W2'82) shows that the defect is a mutation that arose during the long-term cultivation of asexual stages in vitro. Light and electron microscopic images, and indirect immunofluorescence assays with male-specific anti-alpha- tubulin II antibodies, indicate a global disruption of male development at the gametocyte level with at least a 70-90% reduction in the proportion of mature male gametocytes by the Dd2 clone relative to W2'82. A high prevalence of abnormal gametocyte forms, frequently containing multiple and unusually large vacuoles, is associated with the defect. The reduced production of mature male gametocytes may reflect a problem in processes that commit a gametocyte to male development or a progressive attrition of viable male gametocytes during maturation. The defect is genetically linked to an almost complete absence of male gamete production and of infectivity to mosquitoes. This is the first sex-specific developmental mutation identified and characterized in Plasmodium.