Azadirachtin disrupts formation of organised microtubule arrays during microgametogenesis of Plasmodium berghei
Azadirachtin disrupts formation of organised microtubule arrays during microgametogenesis of Plasmodium berghei
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DOI：
10.1111/j.1550-7408.2002.tb00234.x
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发表时间：
2002-11-01
影响因子：
2.2
通讯作者：
Sinden, RE
中科院分区：
文献类型：
--
作者：
Billker, O;Shaw, MK;Sinden, RE
疟疾寄生虫从脊椎动物血液到蚊子媒介的传播关键取决于配子母细胞向配子的分化。这是由于蚊子血粉中的寄生虫受到环境刺激而产生的。雄性配子发生涉及三轮DNA复制和核内有丝分裂，以及8个活动轴丝的重新组装。印楝素是一种作用方式未知的植物类和杀虫剂，特异性地抑制活化的小配子体释放活动配子，但不抑制无性血液阶段的生长和复制。我们结合共聚焦激光扫描显微镜和透射电子显微镜检查印楝素的影响，复杂的重组过程中的微管细胞骨架在疟原虫berghei。印楝素既不能阻止基因组的复制，也不能阻止微管蛋白单体在配子体活化后组装成微管的能力。然而，药物干扰有丝分裂纺锤体的形成和微管组装成典型的轴丝。我们的观察结果表明，azadarachtin专门破坏微管的图案形成更复杂的结构，如有丝分裂纺锤体和轴丝。
Transmission of malaria parasites from vertebrate blood to the mosquito vector depends critically on the differentiation of the gametocytes into gametes. This occurs in response to environmental stimuli encountered by the parasite in the mosquito bloodmeal. Male gametogenesis involves three rounds of DNA replication and endomitosis, and the assembly de novo of 8 motile axonemes. Azadirachtin, a plant limnoid and insecticide with an unkown mode of action, specifically inhibits the release of motile gametes from activated microgametocytes but does not inhibit growth and replication of asexual blood stages. We have combined confocal laser scanning microscopy and transmission electron microscopy to examine the effect of azadirachtin on the complex reorganisation of the microtubule cytoskeleton during gametogenesis in Plasmodium berghei. Neither the replication of the genome nor the ability of tubulin monomers to assemble into microtubules upon gametocyte activation were prevented by azadirachtin. However, the drug interfered with the formation of mitotic spindles and with the assembly of microtubules into typical axonemes. Our observations suggest that azadarachtin specifically disrupts the patterning of microtubules into more complex structures, such as mitotic spindles and axonemes.