Genome-wide functional analysis of Plasmodium protein phosphatases reveals key regulators of parasite development and differentiation.
Genome-wide functional analysis of Plasmodium protein phosphatases reveals key regulators of parasite development and differentiation.
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DOI：
10.1016/j.chom.2014.05.020
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发表时间：
2014-07-09
影响因子：
30.3
通讯作者：
Tewari R
中科院分区：
文献类型：
--
作者：
Guttery DS;Poulin B;Ramaprasad A;Wall RJ;Ferguson DJ;Brady D;Patzewitz EM;Whipple S;Straschil U;Wright MH;Mohamed AM;Radhakrishnan A;Arold ST;Tate EW;Holder AA;Wickstead B;Pain A;Tewari R
由激酶和磷酸酶调控的可逆蛋白质磷酸化控制着许多细胞过程。尽管已报道了疟原虫激酶组的基本功能，但大多数蛋白质磷酸酶（PPs）在疟原虫发育过程中的作用尚不清楚。我们报道了伯氏疟原虫蛋白质磷酸酶组的功能分析，它与恶性疟原虫磷酸酶组具有高度保守性，包含30种预测的蛋白质磷酸酶，在生命周期的各个阶段具有不同且独特的表达模式。对伯氏疟原虫蛋白质磷酸酶的基因破坏分析表明，一半的基因可能对无性血液阶段发育至关重要，而有6个基因是蚊子中进行有性发育/孢子生殖所必需的。表型筛选结合转录组测序揭示了两种N -豆蔻酰化蛋白质磷酸酶缺失突变体的形态变化和基因表达改变。这些发现提供了疟原虫中蛋白质磷酸酶的系统性功能分析，确定了磷酸酶如何调控疟原虫的发育和分化，并可为疟疾药物靶点的确定提供信息。
系统发育分析确定了30种伯氏疟原虫蛋白质磷酸酶（PPs）
功能分析揭示了6种蛋白质磷酸酶在有性发育/孢子生殖中的作用
两种N -豆蔻酰化蛋白质磷酸酶在性别分配和疟原虫传播中起关键作用
RNA - Seq突出显示了N -豆蔻酰化蛋白质磷酸酶突变体中显著改变的基因簇
由激酶和磷酸酶调控的蛋白质磷酸化在疟原虫生命周期中起重要作用。通过进行全基因组功能筛选，格特里等人研究了伯氏疟原虫中的蛋白质磷酸酶，并确定了对宿主血液中无性发育可能至关重要的磷酸酶以及蚊子中有性/孢子生殖发育所必需的磷酸酶。
Reversible protein phosphorylation regulated by kinases and phosphatases controls many cellular processes. Although essential functions for the malaria parasite kinome have been reported, the roles of most protein phosphatases (PPs) during Plasmodium development are unknown. We report a functional analysis of the Plasmodium berghei protein phosphatome, which exhibits high conservation with the P. falciparum phosphatome and comprises 30 predicted PPs with differential and distinct expression patterns during various stages of the life cycle. Gene disruption analysis of P. berghei PPs reveals that half of the genes are likely essential for asexual blood stage development, whereas six are required for sexual development/sporogony in mosquitoes. Phenotypic screening coupled with transcriptome sequencing unveiled morphological changes and altered gene expression in deletion mutants of two N-myristoylated PPs. These findings provide systematic functional analyses of PPs in Plasmodium, identify how phosphatases regulate parasite development and differentiation, and can inform the identification of drug targets for malaria. Phylogenetic analysis identifies 30 Plasmodium berghei protein phosphatases (PPs) Functional analysis reveals role for six PPs in sexual development/sporogony Two N-myristoylated PPs play key roles in sex allocation and parasite transmission RNA-Seq highlights significantly altered gene clusters in the N-myristoylated PP mutants Protein phosphorylation regulated by kinases and phosphatases plays important roles in the Plasmodium life cycle. By performing a genome-wide functional screen, Guttery et al. examine protein phosphatases in Plasmodium berghei and identify phosphatases likely essential for asexual development in host blood as well as those required for sexual/sporogony development in mosquitos.
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影响因子：
4.8
作者：
Baum, J;Richard, D;Cowman, AF
通讯作者：
Cowman, AF
疟原虫中具有 kelch 样结构域 (PPKL) 的独特蛋白磷酸酶可调节动动体分化、运动和侵袭。
影响因子：
6.7
作者：
Guttery DS;Poulin B;Ferguson DJ;Szöőr B;Wickstead B;Carroll PL;Ramakrishnan C;Brady D;Patzewitz EM;Straschil U;Solyakov L;Green JL;Sinden RE;Tobin AB;Holder AA;Tewari R
通讯作者：
Tewari R
影响因子：
64.8
作者：
Reece, Sarah E.;Drew, Damien R.;Gardner, Andy
通讯作者：
Gardner, Andy
影响因子：
3.6
作者：
Mamoun, CB;Gluzman, IY;Goldberg, DE
通讯作者：
Goldberg, DE
影响因子：
8.8
作者：
Patzewitz EM;Guttery DS;Poulin B;Ramakrishnan C;Ferguson DJ;Wall RJ;Brady D;Holder AA;Szöőr B;Tewari R
通讯作者：
Tewari R