Identification of an AP2-family protein that is critical for malaria liver stage development.
Identification of an AP2-family protein that is critical for malaria liver stage development.
复制标题
DOI：
10.1371/journal.pone.0047557
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yuda M
中科院分区：
文献类型：
--
作者：
Iwanaga S;Kaneko I;Kato T;Yuda M
肝期疟原虫是抗疟疾感染药物和疫苗的一个有希望的靶点。然而，目前对这一阶段的基因调控知之甚少。在这项研究中，我们使用的啮齿动物疟疾寄生虫伯氏疟原虫，并表明，AP2家族的转录因子，指定AP2-L，在肝脏阶段的寄生虫的发展中起着至关重要的作用。AP2-L耗尽的寄生虫在血液和蚊子中正常增殖。然而，这些寄生虫感染肝脏的能力比野生型寄生虫低约10，000倍。体外试验表明，这些寄生虫的子孢子正常侵入肝细胞，但它们的发展停止在中间的肝吸虫阶段。使用转基因伯氏疟原虫的表达谱显示，荧光蛋白标记的AP 2-L在肝小体阶段迅速增加，但随着成熟肝小体的形成而突然消失。DNA微阵列分析表明，几个基因的表达，包括那些寄生虫空泡膜蛋白，显着下降，在早期肝脏阶段的AP 2-L耗尽的寄生虫。研究这种转录因子的作用靶点将极大地促进肝期抗原的探索和疟原虫感染肝细胞机制的阐明。
Liver-stage malaria parasites are a promising target for drugs and vaccines against malaria infection. However, little is currently known about gene regulation in this stage. In this study, we used the rodent malaria parasite Plasmodium berghei and showed that an AP2-family transcription factor, designated AP2-L, plays a critical role in the liver-stage development of the parasite. AP2-L-depleted parasites proliferated normally in blood and in mosquitoes. However, the ability of these parasites to infect the liver was approximately 10,000 times lower than that of wild-type parasites. In vitro assays showed that the sporozoites of these parasites invaded hepatocytes normally but that their development stopped in the middle of the liver schizont stage. Expression profiling using transgenic P. berghei showed that fluorescent protein-tagged AP2-L increased rapidly during the liver schizont stage but suddenly disappeared with the formation of the mature liver schizont. DNA microarray analysis showed that the expression of several genes, including those of parasitophorous vacuole membrane proteins, was significantly decreased in the early liver stage of AP2-L-depleted parasites. Investigation of the targets of this transcription factor should greatly promote the exploration of liver-stage antigens and the elucidation of the mechanisms of hepatocyte infection by malaria parasites.
登录
查看更多内容
影响因子：
3.6
作者：
Aly, Ahmed S. I.;Mikolajczak, Sebastian A.;Rivera, Hilda Silva;Camargo, Nelly;Jacobs-Lorena, Vanessa;Labaied, Mehdi;Coppens, Isabelle;Kappe, Stefan H. I.
通讯作者：
Kappe, Stefan H. I.
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
影响因子：
30.3
作者：
Butler NS;Schmidt NW;Vaughan AM;Aly AS;Kappe SH;Harty JT
通讯作者：
Harty JT
影响因子：
14.9
作者：
Balaji S;Babu MM;Iyer LM;Aravind L
通讯作者：
Aravind L
影响因子：
64.8
作者：
Mueller, AK;Labaied, M;Matuschewski, K
通讯作者：
Matuschewski, K