De Novo Synthesis of Phosphatidylcholine Is Essential for the Promastigote But Not Amastigote Stage in Leishmania major.
De Novo Synthesis of Phosphatidylcholine Is Essential for the Promastigote But Not Amastigote Stage in Leishmania major.
复制标题
DOI：
10.3389/fcimb.2021.647870
复制
发表时间：
2021
影响因子：
5.7
通讯作者：
Zhang K
中科院分区：
文献类型：
--
作者：
Moitra S;Basu S;Pawlowic M;Hsu FF;Zhang K
磷脂酰胆碱（PC）是真核生物中最丰富的磷脂类型，占利什曼原虫总脂质的约30%。PC的合成主要通过肯尼迪途径的胆碱分支（胆碱-胆碱-磷酸-CDP-胆碱-PC）和磷脂酰乙醇胺（PE）的N-甲基化进行。此外，利什曼原虫寄生虫可以从宿主或培养基中获得PC和其他脂质。在这项研究中，我们评估的胆碱乙醇胺磷酸转移酶（CEPT）在利什曼原虫主要负责的PC和PE的从头合成的最后一步的功能和必要性。我们的数据表明，CEPT是本地化的内质网，并具有活性，以产生PC从CDP-胆碱和甘油二酯。只有在前鞭毛体阶段存在附加型CEPT基因的情况下，CEPT的靶向缺失才是可能的。少校这些染色体无效的寄生虫需要CEPT的附加型表达才能在培养物中存活，证实了其在前鞭毛体阶段的重要性。与此相反，在体内感染BALB/c小鼠，这些染色体无效的寄生虫似乎失去了附加型副本的CEPT，同时保持正常水平的毒力，复制和细胞PC。因此，虽然PC/PE的从头合成对于前鞭毛体的增殖是必不可少的，但细胞内无鞭毛体似乎通过挽救和重塑获得其大部分脂质。
Phosphatidylcholine (PC) is the most abundant type of phospholipids in eukaryotes constituting ~30% of total lipids in Leishmania. PC synthesis mainly occurs via the choline branch of the Kennedy pathway (choline ⇒ choline-phosphate ⇒ CDP-choline ⇒ PC) and the N-methylation of phosphatidylethanolamine (PE). In addition, Leishmania parasites can acquire PC and other lipids from the host or culture medium. In this study, we assessed the function and essentiality of choline ethanolamine phosphotransferase (CEPT) in Leishmania major which is responsible for the final step of the de novo synthesis of PC and PE. Our data indicate that CEPT is localized in the endoplasmic reticulum and possesses the activity to generate PC from CDP-choline and diacylglycerol. Targeted deletion of CEPT is only possible in the presence of an episomal CEPT gene in the promastigote stage of L. major. These chromosomal null parasites require the episomal expression of CEPT to survive in culture, confirming its essentiality during the promastigote stage. In contrast, during in vivo infection of BALB/c mice, these chromosomal null parasites appeared to lose the episomal copy of CEPT while maintaining normal levels of virulence, replication and cellular PC. Therefore, while the de novo synthesis of PC/PE is indispensable for the proliferation of promastigotes, intracellular amastigotes appear to acquire most of their lipids through salvage and remodeling.
登录
查看更多内容
影响因子：
3.6
作者：
Castanys-Munoz, Esther;Alder-Baerens, Nele;Castanys, Santiago
通讯作者：
Castanys, Santiago
影响因子：
2.3
作者：
Hsu, Fong-Fu;Kuhlmann, F. Matthew;Beverley, Stephen M.
通讯作者：
Beverley, Stephen M.
影响因子：
9.6
作者：
Das, S;Castillo, C;Stevens, T
通讯作者：
Stevens, T
影响因子：
4.6
作者：
Farine L;Niemann M;Schneider A;Bütikofer P
通讯作者：
Bütikofer P
影响因子：
6.4
作者：
Inbar E;Hughitt VK;Dillon LA;Ghosh K;El-Sayed NM;Sacks DL
通讯作者：
Sacks DL