Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite.
Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite.
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DOI：
10.1038/ncomms10519
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发表时间：
2016-01-22
影响因子：
16.6
通讯作者：
Kooij TW
中科院分区：
文献类型：
--
作者：
Kenthirapalan S;Waters AP;Matuschewski K;Kooij TW
孤儿膜转运蛋白的功能和优先考虑候选物进行详细的生物化学表征仍然是根本的挑战，并且对于医学相关的病原体，如疟疾寄生虫特别重要。在这里，我们提出了一个全面的基因分析35孤儿运输蛋白的伯氏疟原虫在其生命周期中的小鼠和按蚊。六个基因，包括四个候选的氨基磷脂转运蛋白，是难治性基因缺失，指示的基本功能。我们产生了29种缺失单个转运蛋白基因的突变株并进行了表型表征。而七个基因似乎是在测试的实验条件下，删除任何其他22个基因导致特定的缺陷，在体内和/或宿主转换的生命周期进展。我们的研究为重金属稳态和宿主转换之间的潜在联系提供了越来越多的支持，并揭示了合理设计新的疟疾干预策略的潜在目标。 疟原虫的许多假定的膜转运蛋白的功能是未知的。在这里，Kenthirapalan等人使用携带靶向基因缺失的突变株来研究35种此类蛋白在蚊子和小鼠宿主中伯氏疟原虫生命周期中的功能。
Assigning function to orphan membrane transport proteins and prioritizing candidates for detailed biochemical characterization remain fundamental challenges and are particularly important for medically relevant pathogens, such as malaria parasites. Here we present a comprehensive genetic analysis of 35 orphan transport proteins of Plasmodium berghei during its life cycle in mice and Anopheles mosquitoes. Six genes, including four candidate aminophospholipid transporters, are refractory to gene deletion, indicative of essential functions. We generate and phenotypically characterize 29 mutant strains with deletions of individual transporter genes. Whereas seven genes appear to be dispensable under the experimental conditions tested, deletion of any of the 22 other genes leads to specific defects in life cycle progression in vivo and/or host transition. Our study provides growing support for a potential link between heavy metal homeostasis and host switching and reveals potential targets for rational design of new intervention strategies against malaria. The functions of many putative membrane transport proteins of malaria parasites are unknown. Here, Kenthirapalan et al. use mutant strains carrying targeted gene deletions to study the functions of 35 such proteins during the life cycle of Plasmodium berghei in mosquito and mouse hosts.