PfAP2-G2 Is Associated to Production and Maturation of Gametocytes in Plasmodium falciparum via Regulating the Expression of PfMDV-1.
PfAP2-G2 Is Associated to Production and Maturation of Gametocytes in Plasmodium falciparum via Regulating the Expression of PfMDV-1.
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DOI：
10.3389/fmicb.2020.631444
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发表时间：
2020
影响因子：
5.2
通讯作者：
Cao Y
中科院分区：
文献类型：
--
作者：
Xu Y;Qiao D;Wen Y;Bi Y;Chen Y;Huang Z;Cui L;Guo J;Cao Y
配子细胞是恶性疟原虫的唯一形式，它可以传播给蚊子载体。本研究发现，apiccomplexan aptala2 （ApiAP2）家族转录因子PfAP2-G2 （Pf3D7_1408200）通过调节PfMDV-1 （Pf3D7_1216500）的表达，在恶性疟原虫配子细胞的发育中发挥作用。逆转录-定量PCR （RT-qPCR）分析显示PfAP2-G2在环期高表达。间接免疫荧光检测显示PfAP2-G2在无性生殖期的核定位。敲除PfAP2-G2导致成熟配子细胞数量减少95%，对雄性配子细胞的产生和成熟有更大的影响，导致雌性/雄性配子细胞比例升高。为了测试这种表型的机制，RNA-seq和RT-qPCR显示，PfAP2-G2的破坏导致雄性发育基因-1 （PfMDV-1）在无性繁殖阶段下调。通过染色质免疫沉淀和qPCR检测，我们进一步发现PfAP2-G2在PfMDV-1的转录起始位点（TSS）富集，这表明PfMDV-1是PfAP2-G2的靶点之一。此外，RT-qPCR还显示，PfAP2-G2敲除寄生虫在分裂体期也下调了性承诺的主调控因子PfAP2-G (Pf3D7_1222600)，但在环期没有变化。这一现象提示PfAP2-G2在寄生虫配子细胞无性发育阶段发挥作用，值得进一步研究PfAP2-G2的调控途径。
Gametocyte is the sole form of the Plasmodium falciparum which is transmissible to the mosquito vector. Here, we report that an Apicomplexan Apetala2 (ApiAP2) family transcription factor, PfAP2-G2 (Pf3D7_1408200), plays a role in the development of gametocytes in P. falciparum by regulating the expression of PfMDV-1 (Pf3D7_1216500). Reverse transcriptase-quantitative PCR (RT-qPCR) analysis showed that PfAP2-G2 was highly expressed in the ring stage. Indirect immunofluorescence assay showed nuclear localization of PfAP2-G2 in asexual stages. The knockout of PfAP2-G2 led to a ~95% decrease in the number of mature gametocytes with a more substantial influence on the production and maturation of the male gametocytes, resulting in a higher female/male gametocyte ratio. To test the mechanism of this phenotype, RNA-seq and RT-qPCR showed that disruption of PfAP2-G2 led to the down-regulation of male development gene-1 (PfMDV-1) in asexual stages. We further found that PfAP2-G2 was enriched at the transcriptional start site (TSS) of PfMDV-1 by chromatin immunoprecipitation and qPCR assay in both ring stage and schizont stage, which demonstrated that PfMDV-1 is one of the targets of PfAP2-G2. In addition, RT-qPCR also showed that PfAP2-G (Pf3D7_1222600), the master regulator for sexual commitment, was also down-regulated in the PfAP2-G2 knockout parasites in the schizont stage, but no change in the ring stage. This phenomenon suggested that PfAP2-G2 played a role at the asexual stage for the development of parasite gametocytes and warrants further investigations in regulatory pathways of PfAP2-G2.
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DOI：
10.1083/jcb.135.1.269
发表时间：
1996-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Guinet F;Dvorak JA;Fujioka H;Keister DB;Muratova O;Kaslow DC;Aikawa M;Vaidya AB;Wellems TE
通讯作者：
Wellems TE
恶性疟原虫网状蛋白相关的衔接蛋白2的MU亚基在体外寄生虫对青蒿素和奎宁的反应调节。
影响因子：
4.9
作者：
Henriques G;van Schalkwyk DA;Burrow R;Warhurst DC;Thompson E;Baker DA;Fidock DA;Hallett R;Flueck C;Sutherland CJ
通讯作者：
Sutherland CJ
影响因子：
4.6
作者：
Martins RM;Macpherson CR;Claes A;Scheidig-Benatar C;Sakamoto H;Yam XY;Preiser P;Goel S;Wahlgren M;Sismeiro O;Coppée JY;Scherf A
通讯作者：
Scherf A
parvum parvum apiap2基因家族：对Apicomplexan AP2调节系统的演变的见解。
影响因子：
14.9
作者：
Oberstaller J;Pumpalova Y;Schieler A;Llinás M;Kissinger JC
通讯作者：
Kissinger JC
影响因子：
6.7
作者：
Campbell TL;De Silva EK;Olszewski KL;Elemento O;Llinás M
通讯作者：
Llinás M