Plasmodium falciparum STEVOR phosphorylation regulates host erythrocyte deformability enabling malaria parasite transmission
Plasmodium falciparum STEVOR phosphorylation regulates host erythrocyte deformability enabling malaria parasite transmission
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DOI：
10.1182/blood-2016-01-690776
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发表时间：
2016-06-16
期刊：
影响因子：
20.3
通讯作者：
Lavazec, Catherine
中科院分区：
文献类型：
--
作者：
Naissant, Bernina;Dupuy, Florian;Lavazec, Catherine
恶性疟原虫配子体感染的红细胞（GIE）的变形性使它们能够在血液循环中持续数天，并确保传播给蚊子。在这里，我们调查的机制，寄生虫蛋白STEVOR（亚TElomeric可变开放阅读框架）施加的GIE变形性的变化。使用微量离心法，免疫沉淀和质谱，我们产生的证据表明，GIE刚度是依赖于细胞质结构域的STEVOR相互作用与锚蛋白复合物在红细胞骨架。此外，我们表明，GIE变形性调节蛋白激酶A（PKA）介导的磷酸化STEVOR C-末端结构域在一个特定的丝氨酸残基（S-324）。最后，我们发现西地那非（伟哥）诱导的GIE僵硬度增加依赖于STEVOR磷酸化状态和另一种独立机制。这些数据为磷酸二酯酶抑制剂阻断疟原虫传播的机制提供了新的见解。
Deformability of Plasmodium falciparum gametocyte-infected erythrocytes (GIEs) allows them to persist for several days in blood circulation and to ensure transmission to mosquitoes. Here, we investigate the mechanism by which the parasite proteins STEVOR (SubTElomeric Variable Open Reading frame) exert changes on GIE deformability. Using the microsphiltration method, immunoprecipitation, and mass spectrometry, we produce evidence that GIE stiffness is dependent on the cytoplasmic domain of STEVOR that interacts with ankyrin complex at the erythrocyte skeleton. Moreover, we show that GIE deformability is regulated by protein kinase A (PKA)-mediated phosphorylation of the STEVOR C-terminal domain at a specific serine residue (S-324). Finally, we show that the increase of GIE stiffness induced by sildenafil (Viagra) is dependent on STEVOR phosphorylation status and on another independent mechanism. These data provide new insights into mechanisms by which phosphodiesterase inhibitors may block malaria parasite transmission.