Protein phosphatase 1, a Plasmodium falciparum essential enzyme, is exported to the host cell and implicated in the release of infectious merozoites
Protein phosphatase 1, a Plasmodium falciparum essential enzyme, is exported to the host cell and implicated in the release of infectious merozoites
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DOI：
10.1111/j.1462-5822.2005.00650.x
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发表时间：
2006-04-01
影响因子：
3.4
通讯作者：
Braun-Breton, C
中科院分区：
文献类型：
--
作者：
Blisnick, T;Vincensini, L;Braun-Breton, C
疟疾寄生虫恶性疟原虫将高尔基体样隔室（称为Maurer's clefts）转移到其宿主细胞红细胞的细胞质中，并将寄生虫分子传递到宿主细胞表面。我们在这里报告一个新的作用毛雷尔的裂缝牵连的寄生虫蛋白磷酸酶1（PP1）和相关的磷酸化状态的恶性疟原虫疟原虫粘附分子结合蛋白1（PfSBP 1），跨膜蛋白的裂缝通过其羧基末端结构域与宿主细胞膜相互作用。基于免疫共沉淀和抑制的研究，我们表明，寄生虫PP1型磷酸酶调节Maurer's裂腔PfSBP1的氨基末端结构域的磷酸化状态。重要的是，在晚期寄生虫中加入PP1抑制剂calyculin A会导致PfSBP 1的过度磷酸化，并阻止寄生虫从宿主细胞中释放。我们提出PfSBP 1的过度磷酸化通过增加红细胞膜的稳定性来干扰裂殖子的释放，裂殖子是寄生虫的侵入性血液阶段。此外，寄生虫PP1磷酸酶是在毛雷尔氏裂中检测到的寄生虫发育所必需的第一种酶。
The malarial parasite Plasmodium falciparumTransposes a Golgi-like compartment, referred to as Maurer's clefts, into the cytoplasm of its host cell, the erythrocyte, and delivering parasite molecules to the host cell surface. We report here a novel role of the Maurer's clefts implicating a parasite protein phosphatase 1 (PP1) and related to the phosphorylation status of P. falciparum skeleton-binding protein 1 (PfSBP1), a trans-membrane protein of the clefts interacting with the host cell membrane via its carboxy-terminal domain. Based on coimmunoprecipitation and inhibition studies, we show that the parasite PP1 type phosphatase modulates the phosphorylation status of the amino-terminal domain of PfSBP1 in the lumen of Maurer's clefts. Importantly, the addition of a PP1 inhibitor, calyculin A, to late schizonts results in the hyperphosphorylation of PfSBP1 and prevents parasite release from the host cell. We propose that the hyperphosphorylation of PfSBP1 interferes with the release of merozoites, the invasive blood stage of the parasite, by increasing the red cell membrane stability. Moreover, the parasite PP1 phosphatase is the first enzyme essential for the parasite development detected in the Maurer's clefts.