A patatin-like phospholipase functions during gametocyte induction in the malaria parasite Plasmodium falciparum
A patatin-like phospholipase functions during gametocyte induction in the malaria parasite Plasmodium falciparum
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DOI：
10.1111/cmi.13146
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发表时间：
2020-03-01
影响因子：
3.4
通讯作者：
Pradel, Gabriele
中科院分区：
文献类型：
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作者：
Flammersfeld, Ansgar;Panyot, Atscharah;Pradel, Gabriele
Patatin-like phospholipases （PNPLAs）是原核生物和真核生物中高度保守的酶，在脂质稳态中起重要作用。疟原虫恶性疟原虫的基因组编码四个假定的pnpla，它们在磷脂降解过程中具有预测的功能。我们在此研究了一种被称为PNPLA1的疟原虫pnpla(2)在血期复制和配子细胞发育过程中的作用。PNPLA1存在于无性和有性血液阶段，在这里定位于细胞质。pnpla1因基因破坏或条件性基因敲低而缺乏对红细胞生长、配子细胞发育和配子发生没有影响。然而，缺乏PNPLA1的寄生虫在配子体诱导中受损，而PNPLA1过表达促进配子体形成。PNPLA1的缺失进一步导致配子细胞发生相关基因的转录下调，包括编码性承诺调节因子AP2-G的基因。此外，缺乏pnpla1的无性血期寄生虫的脂质组学显示，主要磷脂水平总体升高，包括磷脂酰胆碱（PC），它是PLA的底物(2)。众所周知，PC合成是红细胞复制的关键，而PC前体可用性的降低驱使寄生虫进入配子细胞发生；因此，我们假设pnpla1缺乏导致的PC水平升高阻止了血期寄生虫进入性途径。
Patatin-like phospholipases (PNPLAs) are highly conserved enzymes of prokaryotic and eukaryotic organisms with major roles in lipid homeostasis. The genome of the malaria parasite Plasmodium falciparum encodes four putative PNPLAs with predicted functions during phospholipid degradation. We here investigated the role of one of the plasmodial PNPLAs, a putative PLA(2) termed PNPLA1, during blood stage replication and gametocyte development. PNPLA1 is present in the asexual and sexual blood stages and here localizes to the cytoplasm. PNPLA1-deficiency due to gene disruption or conditional gene-knockdown had no effect on intraerythrocytic growth, gametocyte development and gametogenesis. However, parasites lacking PNPLA1 were impaired in gametocyte induction, while PNPLA1 overexpression promotes gametocyte formation. The loss of PNPLA1 further leads to transcriptional down-regulation of genes related to gametocytogenesis, including the gene encoding the sexual commitment regulator AP2-G. Additionally, lipidomics of PNPLA1-deficient asexual blood stage parasites revealed overall increased levels of major phospholipids, including phosphatidylcholine (PC), which is a substrate of PLA(2). PC synthesis is known to be pivotal for erythrocytic replication, while the reduced availability of PC precursors drives the parasite into gametocytogenesis; we thus hypothesize that the higher PC levels due to PNPLA1-deficiency prevent the blood stage parasites from entering the sexual pathway.