Identification and characterization of stearoyl-CoA desaturase in Toxoplasma gondii
Identification and characterization of stearoyl-CoA desaturase in Toxoplasma gondii
复制标题
弓形虫中硬脂酰辅酶A去饱和酶的鉴定和表征
DOI：
10.1093/abbs/gmz040
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发表时间：
2019
影响因子：
3.7
通讯作者：
Liul Qun
中科院分区：
文献类型：
--
作者：
Hao Pan;Cui Xia;Liu Jing;Li Muzi;Fu Yong;Liul Qun
Few information of the function of stearoyl-coenzyme A (CoA) desaturase (SCD) in apicomplaxan parasite has been obtained. In this study, we retrieved a putative fatty acyl-CoA desaturase (TGGT1_238950) by a protein alignment withPlasmodium falciparumSCD in ToxoDB. A typical Δ9-desaturase domain was revealed in this protein. The putative desaturase was tagged with HA endogenously inToxoplasma gondii, and the endoplasmic reticulum localization of the putative desaturase was revealed, which was consistent with the fatty acid desaturases in other organisms. Therefore, the TGGT1_238950 was designatedT. gondiiSCD. Based on CRISPR/Cas9 gene editing technology, SCD conditional knockout mutants in theT. gondiiTATi strain were obtained. The growthin vitroand pathogenicity in mice of the mutants suggested that SCD might be dispensable for tachyzoite growth and proliferation. The SCD-overexpressing line was constructed to further explore SCD function. The portion of palmitoleic acid and oleic acid were increased in SCD-overexpressing parasites, compared with the RH parental strain, indicating thatT. gondiiindeed is competent for unsaturated fatty acid synthesis. The SCD-overexpressing tachyzoites propagated slower than the parental strain, with a decreased invasion capability and weaker pathogenicity in mice. The TgIF2α phosphorylation and the expression changes of several genes demonstrated that ER stress was triggered in the SCD-overexpressing parasites, which were more apt toward autophagy and apoptosis. The function of unsaturated fatty acid synthesis of TgSCD was consistent with our hypothesis. On the other hand, SCD might also be involved in tachyzoite autophagy and apoptosis.
