Distinct signalling pathways control Toxoplasma egress and host-cell invasion
Distinct signalling pathways control Toxoplasma egress and host-cell invasion
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DOI：
10.1038/emboj.2012.299
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发表时间：
2012-12-12
期刊：
影响因子：
11.4
通讯作者：
Sibley, L. David
中科院分区：
文献类型：
--
作者：
Lourido, Sebastian;Tang, Keliang;Sibley, L. David
钙信号协调运动，细胞入侵，和出口的apicomplexan寄生虫，但关键的介质，这些信号仍然在很大程度上未知。一个潜在的假设是，入侵和从宿主细胞的出口依赖于高度相似的系统启动运动。使用化学遗传学的方法来特异性地抑制选择的钙依赖性激酶（CDPKs），我们反而证明，这些途径是由不同的激酶控制：TgCDPK 1和TgCDPK 3都需要在离子载体诱导的出口，但只有TgCDPK 1需要在入侵。同样，微线体分泌，这是必要的运动过程中的入侵和出口，普遍依赖于TgCDPK 1，但只有表现出TgCDPK 3的依赖性时，触发某些刺激。我们还表明，出口可能受到环GMP依赖性蛋白激酶的进一步控制，其激活可以诱导出口，并部分补偿TgCDPK 3的抑制。这些结果表明，单独的信号转导通路被整合，以调节运动性，以响应不同的信号，促进入侵或出口期间感染弓形虫。The EMBO Journal（2012）31，4524-4534. doi：10.1038/doj.2012.299; 2012年11月13日在线发布
Calcium signalling coordinates motility, cell invasion, and egress by apicomplexan parasites, yet the key mediators that transduce these signals remain largely unknown. One underlying assumption is that invasion into and egress from the host cell depend on highly similar systems to initiate motility. Using a chemical-genetic approach to specifically inhibit select calcium-dependent kinases (CDPKs), we instead demonstrate that these pathways are controlled by different kinases: both TgCDPK1 and TgCDPK3 were required during ionophore-induced egress, but only TgCDPK1 was required during invasion. Similarly, microneme secretion, which is necessary for motility during both invasion and egress, universally depended on TgCDPK1, but only exhibited TgCDPK3 dependence when triggered by certain stimuli. We also demonstrate that egress likely comes under a further level of control by cyclic GMP-dependent protein kinase and that its activation can induce egress and partially compensate for the inhibition of TgCDPK3. These results demonstrate that separate signalling pathways are integrated to regulate motility in response to the different signals that promote invasion or egress during infection by Toxoplasma gondii. The EMBO Journal (2012) 31, 4524-4534. doi: 10.1038/emboj.2012.299; Published online 13 November 2012