PDF(Pubmed)
Abstract：
Glycerophospholipids have emerged as a significant contributor to the intracellular growth of pathogenic protist Toxoplasma gondii. Phosphatidylserine (PtdSer) is one such lipid, attributed to the locomotion and motility-dependent invasion and egress events in its acutely infectious tachyzoite stage. However, the de novo synthesis of PtdSer and the importance of the pathway in tachyzoites remain poorly understood. We show that a base-exchange-type PtdSer synthase (PSS) located in the parasite\'s endoplasmic reticulum produces PtdSer, which is rapidly converted to phosphatidylethanolamine (PtdEtn) by PtdSer decarboxylase (PSD) activity. The PSS-PSD pathway enables the synthesis of several lipid species, including PtdSer (16:0/18:1) and PtdEtn (18:2/20:4, 18:1/18:2 and 18:2/22:5). The PSS-depleted strain exhibited a lower abundance of the major ester-linked PtdEtn species and concurrent accrual of host-derived ether-PtdEtn species. Most phosphatidylthreonine (PtdThr) species-an exclusive natural analog of PtdSer, also made in the endoplasmic reticulum-were repressed. PtdSer species, however, remained largely unaltered, likely due to the serine-exchange reaction of PtdThr synthase in favor of PtdSer upon PSS depletion. Not least, the loss of PSS abrogated the lytic cycle of tachyzoites, impairing the cell division, motility, and egress. In a nutshell, our data demonstrate a critical role of PSS in the biogenesis of PtdSer and PtdEtn species and its physiologically essential repurposing for the asexual reproduction of a clinically relevant intracellular pathogen.
摘要：
甘油磷脂已成为致病性原生弓形虫细胞内生长的重要因素。磷脂酰丝氨酸（PtdSer）是一种这样的脂质，归因于其急性感染速殖子阶段的运动和运动依赖性入侵和外出事件。然而,PtdSer的从头合成以及该途径在速殖子中的重要性仍然知之甚少。我们显示寄生虫内质网中的碱基交换型PtdSer合酶（PSS）产生PtdSer，其通过PtdSer脱羧酶(PSD)快速转化为磷脂酰乙醇胺(PtdEtn)。PSS-PSD途径能够合成几种物种，包括PtdSer（16：0/18：1）和PtdEtn（18：2/20：4，18：1/18：2和18：2/22：5）。PSS耗尽的菌株显示出主要的酯连接的PtdEtn物种的丰度较低，并且同时产生了宿主衍生的醚-PtdEtn物种。大多数磷脂酰苏氨酸（PtdThr）物种-在内质网中产生的PtdSer的专有天然类似物-被抑制，虽然PtdSer物种基本上没有改变，可能是由PtdThr合酶的丝氨酸交换反应驱动的，在PSS消耗时有利于PtdSer。并非最不重要的,由于细胞分裂受损，PSS的丢失废除了速殖子的裂解周期，运动性,和出口。简而言之，我们的数据证明了PSS在PtdSer和PtdEtn物种的生物发生中的关键作用，以及其在临床相关的细胞内病原体的无性繁殖中的生理上必需的用途。
