Multiple short windows of calcium-dependent protein kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesis
Multiple short windows of calcium-dependent protein kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesis
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DOI：
10.7554/elife.26524
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发表时间：
2017-05-08
期刊：
影响因子：
7.7
通讯作者：
Brochet, Mathieu
中科院分区：
文献类型：
--
作者：
Fang, Hanwei;Klages, Natacha;Brochet, Mathieu
疟疾的传播依赖于蚊子摄入后配子的产生。在这里，我们表明，钙离子依赖性蛋白激酶4控制三个过程必不可少的进步，从一个单一的单倍体小配子体释放8个鞭毛的小配子在伯氏疟原虫。豆蔻酰化同种型被Ca 2+激活，以在激活的20秒内启动第一次基因组复制。这种作用是由参与S期进入的SAP结构域家族的蛋白介导的。同时，CDPK4是随后的有丝分裂纺锤体组装和磷酸化微管相关蛋白所必需的，微管相关蛋白对有丝分裂纺锤体的形成很重要。最后，一个非豆蔻酰化的亚型是必不可少的，以完成胞质分裂激活运动的男性鞭毛。这种作用与一种未表征的鞭毛蛋白的磷酸化有关。总之，这项研究揭示了激酶如何整合和转导多种信号，以控制疟原虫配子发生过程中的关键细胞周期转换。
Malaria transmission relies on the production of gametes following ingestion by a mosquito. Here, we show that Ca2+-dependent protein kinase 4 controls three processes essential to progress from a single haploid microgametocyte to the release of eight flagellated microgametes in Plasmodium berghei. A myristoylated isoform is activated by Ca2+ to initiate a first genome replication within twenty seconds of activation. This role is mediated by a protein of the SAPS-domain family involved in S-phase entry. At the same time, CDPK4 is required for the assembly of the subsequent mitotic spindle and to phosphorylate a microtubule-associated protein important for mitotic spindle formation. Finally, a non-myristoylated isoform is essential to complete cytokinesis by activating motility of the male flagellum. This role has been linked to phosphorylation of an uncharacterised flagellar protein. Altogether, this study reveals how a kinase integrates and transduces multiple signals to control key cell-cycle transitions during Plasmodium gametogenesis.