Construction of a Plasmodium falciparum Rab-interactome identifies CK1 and PKA as Rab-effector kinases in malaria parasites.
Construction of a Plasmodium falciparum Rab-interactome identifies CK1 and PKA as Rab-effector kinases in malaria parasites.
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DOI：
10.1111/boc.201100081
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发表时间：
2012-01
影响因子：
2.7
通讯作者：
Langsley G
中科院分区：
文献类型：
--
作者：
Rached FB;Ndjembo-Ezougou C;Chandran S;Talabani H;Yera H;Dandavate V;Bourdoncle P;Meissner M;Tatu U;Langsley G
人类疟疾寄生虫恶性疟原虫的病理致病阶段存在于红细胞中，红细胞缺乏任何受调节的运输系统。因此，寄生虫完全负责介导自身和受感染红细胞胞浆中的囊泡运输，并且部分通过其11个Rab gtp酶家族完成。由于Rabs疟原虫与酵母的Rabs具有同源性，特别是与具有相同数量的rabb /ypt基因的酵母菌具有同源性，并且对ypt功能的分析已经得到了很好的表征。由于Rabs具有招募特定效应物的能力，因此Rabs是囊泡交通的重要调节因子。为了鉴定恶性疟原虫Rab （pfrrab）效应物，我们首先利用Saccharomyces基因组数据库（SGD）的遗传和物理结合数据构建了一个ypt相互作用组。然后，我们利用与ypt效应物同源性鉴定的推定寄生虫rab效应物构建了pfrab相互作用组。我们通过湿台测试三种预测来证明其潜力；酪蛋白激酶-1 （PfCK1）是一种特异性的Rab5B相互作用蛋白，camp依赖性蛋白激酶a （pfka - c）的催化亚基是PfRab5A和PfRab7效应蛋白。一组共享的物理Ypt/ pfrab -效应蛋白的建立，揭示了一组与酵母共享的核心rab -相互作用蛋白。pfrab -相互作用组应该有利于疟疾寄生虫的囊泡贩运研究。PfCK1分别被募集到PfRab5B+和pfka - c分别被募集到PfRab5A+和PfRab7+囊泡，这表明pfrab募集的激酶可能在疟疾寄生虫的早期和晚期内体功能中发挥作用。
The pathology causing stages of the human malaria parasite Plasmodium falciparum reside within red blood cells that are devoid of any regulated transport system. The parasite, therefore, is entirely responsible for mediating vesicular transport within itself and in the infected erythrocyte cytoplasm, and it does so in part via its family of 11 Rab GTPases. Putative functions have been ascribed to Plasmodium Rabs due to their homology with Rabs of yeast, particularly with Saccharomyces that has an equivalent number of rab/ypt genes and where analyses of Ypt function is well characterized. Rabs are important regulators of vesicular traffic due to their capacity to recruit specific effectors. In order to identify P. falciparum Rab (PfRab) effectors, we first built a Ypt-interactome by exploiting genetic and physical binding data available at the Saccharomyces genome database (SGD). We then constructed a PfRab-interactome using putative parasite Rab-effectors identified by homology to Ypt-effectors. We demonstrate its potential by wet-bench testing three predictions; that casein kinase-1 (PfCK1) is a specific Rab5B interacting protein and that the catalytic subunit of cAMP-dependent protein kinase A (PfPKA-C) is a PfRab5A and PfRab7 effector. The establishment of a shared set of physical Ypt/PfRab-effector proteins sheds light on a core set Plasmodium Rab-interactants shared with yeast. The PfRab-interactome should benefit vesicular trafficking studies in malaria parasites. The recruitment of PfCK1 to PfRab5B+ and PfPKA-C to PfRab5A+ and PfRab7+ vesicles, respectively, suggests that PfRab-recruited kinases potentially play a role in early and late endosome function in malaria parasites.
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影响因子：
16.6
作者：
Gruering, Christof;Heiber, Arlett;Spielmann, Tobias
通讯作者：
Spielmann, Tobias
DOI：
10.1073/pnas.0711067105
发表时间：
2008-02-19
影响因子：
11.1
作者：
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1.5
作者：
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影响因子：
3.5
作者：
Quevillon, E;Spielmann, T;Langsley, G
通讯作者：
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影响因子：
5.8
作者：
Langsley G;van Noort V;Carret C;Meissner M;de Villiers EP;Bishop R;Pain A
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