Transition of Plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein Pumilio.
Transition of Plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein Pumilio.
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RNA结合蛋白pumilio调节了疟原虫孢子岩向肝脏阶段形式的过渡。
DOI：
10.1371/journal.ppat.1002046
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发表时间：
2011-05
期刊：
影响因子：
6.7
通讯作者：
Mota MM
中科院分区：
文献类型：
--
作者：
Gomes-Santos CS;Braks J;Prudêncio M;Carret C;Gomes AR;Pain A;Feltwell T;Khan S;Waters A;Janse C;Mair GR;Mota MM
许多真核生物的发育和细胞命运的决定都是转录后影响的，涉及作为关键mRNAs翻译调节因子的RNA结合蛋白。在疟疾寄生虫中，从细长的、运动的和细胞周期受阻的子孢子发育成圆形的、不活动的和复制的红外期肝脏阶段，被认为取决于寄生虫从蚊媒传播到脊椎动物宿主过程中所经历的环境变化。在这里，我们发现疟原虫是RNA结合蛋白家族PUF的一个成员，是这种转化的关键调节因子。在没有Pumilio-2(Puf2)的情况下，子孢子在蚊子唾液腺内启动EEF发育，而不依赖于正常的传播相关环境线索。Puf2-子孢子表现出全基因组的转录变化，导致滑行运动、细胞穿越能力的丧失和感染性的降低，此外，还触发了典型的早期疟原虫肝内发育的变态。这些数据表明Puf2在调节子孢子发育控制中起关键作用，并暗示唾液腺驻留的子孢子向肝期样寄生虫的转化受转录后机制的调控。按蚊将疟原虫子孢子注射到人类宿主体内会引发疟疾感染。导致疾病发病的血液期寄生虫的产生有赖于子孢子在肝脏中成功发育成裂殖子。在这里，我们证明了在伯氏疟原虫的啮齿动物模型中，这些发育转化是由RNA结合蛋白Pumilio 2(Puf2)控制的。在没有Puf2的情况下，子孢子虽然仍然在蚊子的唾液腺中，但在不需要任何环境信号的情况下，会慢慢转变为早期的红外型寄生虫。形态上的早熟变态的特征是内膜复合体的丢失和清晰的突起的产生，这导致了圆形的肝脏期样寄生虫。这种转录变化与子孢子到肝脏阶段的发育过程中发生的发育适应是一致的。总体而言，突变寄生虫中90%的上调基因只在肝期寄生虫蛋白质组中被鉴定，而不是在子孢子蛋白质组中。疟原虫Puf2是Pumillo家族的成员，在许多不同的生物体中参与关键的发育决定，在子孢子从蚊子媒介传播到哺乳动物宿主的过程中，它扮演着一个明确的生命周期进程调节器的角色。
Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism. Injection of Plasmodium sporozoites by Anopheles mosquitoes into the human host initiates malaria infection. Generation of blood stage parasites leading to the onset of disease relies on the successful development of the sporozoite into merozoites in the liver. Here we show that in the rodent malaria model Plasmodium berghei these developmental transformations are controlled by the RNA binding protein Pumilio 2 (Puf2). In the absence of Puf2, sporozoites, while still in the mosquito salivary gland, slowly transform into early stage exo-erythrocytic form parasites without the need for any environmental signals. Morphologically precocious metamorphosis is characterized by the loss of the inner membrane complex and the generation of clear protrusions which result in round liver stage-like parasites. The transcriptional alterations are consistent with developmental adaptations that occur during sporozoite to liver stage-like developmental progression. In total, 90% of up-regulated genes in mutant parasites have only been identified in liver stage parasite proteomes, but not the sporozoite proteome. Plasmodium Puf2, a member of the Pumillo family known to be involved in key developmental decisions in many different organisms, acts as a clear regulator of life cycle progression during sporozoite transmission from the mosquito vector to the mammalian host.
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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：
64.8
作者：
de Koning-Ward, Tania F.;Gilson, Paul R.;Boddey, Justin A.;Rug, Melanie;Smith, Brian J.;Papenfuss, Anthony T.;Sanders, Paul R.;Lundie, Rachel J.;Maier, Alexander G.;Cowman, Alan F.;Crabb, Brendan S.
通讯作者：
Crabb, Brendan S.
DOI：
10.1098/rstb.2003.1333
发表时间：
2003-08-29
期刊：
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
Crittenden, SL;Eckmann, CR;Kimble, J
通讯作者：
Kimble, J
DOI：
10.1084/jem.20022100
发表时间：
2003-04-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kaiser K;Camargo N;Kappe SH
通讯作者：
Kappe SH
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP