Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival.
Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival.
复制标题
DOI：
10.1038/s41467-021-21360-8
复制
发表时间：
2021-02-23
影响因子：
16.6
通讯作者：
Mottram JC
中科院分区：
文献类型：
--
作者：
Baker N;Catta-Preta CMC;Neish R;Sadlova J;Powell B;Alves-Ferreira EVC;Geoghegan V;Carnielli JBT;Newling K;Hughes C;Vojtkova B;Anand J;Mihut A;Walrad PB;Wilson LG;Pitchford JW;Volf P;Mottram JC
不同阶段的分化是细胞内原生动物寄生虫生命周期和宿主间传播的基础，需要严格的时空调控。在这里，我们利用墨西哥利什曼原虫的全基因组基因缺失和基因标记来定义具有生命周期转换作用的蛋白激酶。虽然162个蛋白激酶基因是不可缺少的，但有44个蛋白激酶基因在原毛体中是难以删除的，它们可能是寄生虫复制所需的核心基因。利用bar-seq和投影追踪聚类技术对汇集的基因缺失突变体进行表型分析，揭示了参与从元环promastigote向amastigote分化、巨噬细胞和小鼠的生长和存活、沙蝇的定植和运动的蛋白激酶的功能表型组。这种对利什曼原虫蛋白激酶功能的无偏见的询问允许对成功的细胞内寄生所需的细胞器相关信号通路进行有针对性的调查。蛋白激酶是利什曼原虫在整个生命周期中生存所需的细胞信号传导的基础。在这里，Baker和Catta-Preta等人报道了墨西哥利什曼原虫的一项全激酶功能研究，以确定在生命周期转变中发挥作用的蛋白激酶。
Differentiation between distinct stages is fundamental for the life cycle of intracellular protozoan parasites and for transmission between hosts, requiring stringent spatial and temporal regulation. Here, we apply kinome-wide gene deletion and gene tagging in Leishmania mexicana promastigotes to define protein kinases with life cycle transition roles. Whilst 162 are dispensable, 44 protein kinase genes are refractory to deletion in promastigotes and are likely core genes required for parasite replication. Phenotyping of pooled gene deletion mutants using bar-seq and projection pursuit clustering reveal functional phenotypic groups of protein kinases involved in differentiation from metacyclic promastigote to amastigote, growth and survival in macrophages and mice, colonisation of the sand fly and motility. This unbiased interrogation of protein kinase function in Leishmania allows targeted investigation of organelle-associated signalling pathways required for successful intracellular parasitism. Protein kinases are fundamental in cellular signalling required for Leishmania survival throughout the life cycle. Here, Baker and Catta-Preta et al. report on a kinome-wide functional study in Leishmania mexicana to define protein kinases with roles in life cycle transition.
登录
查看更多内容
影响因子：
6.7
作者：
Burge RJ;Damianou A;Wilkinson AJ;Rodenko B;Mottram JC
通讯作者：
Mottram JC
影响因子：
3.6
作者：
Duncan SM;Myburgh E;Philipon C;Brown E;Meissner M;Brewer J;Mottram JC
通讯作者：
Mottram JC
影响因子：
64.5
作者：
Akiyoshi B;Gull K
通讯作者：
Gull K
影响因子：
9
作者：
Castanys-Munoz, E.;Brown, E.;Mottram, J. C.
通讯作者：
Mottram, J. C.
影响因子：
3.6
作者：
Costa Rocha, Vinicius Pinto;Dacher, Mariko;Smirlis, Despina
通讯作者：
Smirlis, Despina