CDPK2A and CDPK1 form a signaling module upstream of Toxoplasma motility.
CDPK2A and CDPK1 form a signaling module upstream of Toxoplasma motility.
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作者：
在顶复门寄生虫中，复制和传播之间的转换受细胞溶质钙浓度波动的调节，部分由钙依赖性蛋白激酶（CDPKs）转导。我们研究了CDPK 2A在弓形虫裂解周期中的作用，分析了其在调节与寄生虫运动相关的细胞过程中的作用。我们使用化学遗传学方法和条件耗竭，以确定CDPK 2A有助于启动寄生虫运动通过微线放电。我们证明了CDPK 2A的N-末端延伸对于蛋白质的功能是必要的。条件性耗竭揭示了CDPK 2A和CDPK 1之间的上位相互作用，表明这两种激酶共同作用以介导对某些刺激的反应。该信号传导模块似乎与CDPK 3和蛋白激酶G不同，后者也控制出口。CDPK 2A被揭示为弓形虫动力学阶段的重要调节剂，与控制这一关键转变的其他激酶相关。我们的工作揭示了调节寄生虫运动的信号通路之间的广泛相互联系。这项工作揭示了各种信号通路之间的相互作用，治理弓形虫出口。具体来说，我们比较了三个典型的钙依赖性蛋白激酶（CDPKs）的功能，使用化学遗传和条件消耗的方法。我们描述了以前未表征的CDPK，CDPK 2A，在弓形虫裂解周期的功能，表明它有助于寄生虫健身通过调节微线放电，滑翔运动，并从受感染的宿主细胞的出口。类似物敏感的激酶等位基因和条件耗尽的等位基因的比较发现CDPK 2A和CDPK 1之间的上位性，这意味着部分功能冗余。了解寄生虫生命周期中关键事件背后的信号通路拓扑结构可以帮助针对抗寄生虫疗法的激酶的努力。
In apicomplexan parasites, the transition between replication and dissemination is regulated by fluctuations in cytosolic calcium concentrations, transduced in part by calcium-dependent protein kinases (CDPKs). We examined the role of CDPK2A in the lytic cycle of Toxoplasma, analyzing its role in the regulation of cellular processes associated with parasite motility. We used chemical-genetic approaches and conditional depletion to determine that CDPK2A contributes to the initiation of parasite motility through microneme discharge. We demonstrate that the N-terminal extension of CDPK2A is necessary for the protein’s function. Conditional depletion revealed an epistatic interaction between CDPK2A and CDPK1, suggesting that the two kinases work together to mediate motility in response to certain stimuli. This signaling module appears distinct from that of CDPK3 and protein kinase G, which also control egress. CDPK2A is revealed as an important regulator of the Toxoplasma kinetic phase, linked to other kinases that govern this critical transition. Our work uncovers extensive interconnectedness between the signaling pathways that regulate parasite motility. This work uncovers interactions between various signaling pathways that govern Toxoplasma gondii egress. Specifically, we compare the function of three canonical calcium-dependent protein kinases (CDPKs) using chemical-genetic and conditional-depletion approaches. We describe the function of a previously uncharacterized CDPK, CDPK2A, in the Toxoplasma lytic cycle, demonstrating that it contributes to parasite fitness through regulation of microneme discharge, gliding motility, and egress from infected host cells. Comparison of analog-sensitive kinase alleles and conditionally depleted alleles uncovered epistasis between CDPK2A and CDPK1, implying a partial functional redundancy. Understanding the topology of signaling pathways underlying key events in the parasite life cycle can aid in efforts targeting kinases for anti-parasitic therapies.
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影响因子：
6.7
作者：
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