Plasmenylethanolamine synthesis in Leishmania major
Plasmenylethanolamine synthesis in Leishmania major
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DOI：
10.1111/mmi.13387
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发表时间：
2016-07-01
影响因子：
3.6
通讯作者：
Zhang, Kai
中科院分区：
文献类型：
--
作者：
Pawlowic, Mattie C.;Hsu, Fong-fu;Zhang, Kai
乙醇胺甘油磷脂是普遍存在的细胞膜组分。利什曼原虫属的锥虫寄生虫通过Kennedy途径将它们的大部分乙醇胺甘油磷脂合成为1-O-烷-1-烯基-2-酰基-sn-甘油基-3-磷酸乙醇胺或浆烯基乙醇胺（PME）。PME是醚磷脂的一种亚型，也称为乙醇胺缩醛磷脂，其功能尚未得到充分表征。在这项研究中，我们研究了PME合成的作用，利什曼原虫主要通过乙醇胺磷酸转移酶（EPT）突变体的特性。EPT无效寄生虫在很大程度上缺乏PME，在常规培养基中完全存活，但在没有胎牛血清的情况下不能增殖。它们在GPI锚定的表面分子的合成和定位中表现出显著的异常。EPT无效突变体在BALB/c小鼠中也显示出减弱的毒力。此外，除了PME合成，乙醇胺还有助于产生磷脂酰胆碱，这是利什曼原虫中最丰富的一类脂质。总之，这些发现表明，乙醇胺生产可能需要利什曼原虫前鞭毛体产生大量磷脂，处理应力，并控制膜结合的毒力因子的表达。
Ethanolamine glycerophospholipids are ubiquitous cell membrane components. Trypanosomatid parasites of the genus Leishmania synthesize the majority of their ethanolamine glycerophospholipids as 1-O-alk-1-enyl-2-acyl-sn-glycero-3-phosphoethanolamine or plasmenylethanolamine (PME) through the Kennedy pathway. PME is a subtype of ether phospholipids also known as ethanolamine plasmalogen whose functions are not well characterized. In this study, we investigated the role of PME synthesis in Leishmania major through the characterization of an ethanolamine phosphotransferase (EPT) mutant. EPT-null parasites are largely devoid of PME and fully viable in regular medium but fail to proliferate in the absence of fetal bovine serum. They exhibit significant abnormalities in the synthesis and localization of GPI-anchored surface molecules. EPT-null mutants also show attenuated virulence in BALB/c mice. Furthermore, in addition to PME synthesis, ethanolamine also contributes to the production of phosphatidylcholine, the most abundant class of lipids in Leishmania. Together, these findings suggest that ethanolamine production is likely required for Leishmania promastigotes to generate bulk phospholipids, to handle stress, and to control the expression of membrane bound virulence factors.