Plasmodium falciparum GAP40 Plays an Essential Role in Merozoite Invasion and Gametocytogenesis.
Plasmodium falciparum GAP40 Plays an Essential Role in Merozoite Invasion and Gametocytogenesis.
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恶性疟原虫 GAP40 在裂殖子侵袭和配子细胞发生中发挥重要作用。
DOI：
10.1128/spectrum.01434-23
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发表时间：
2023-06-15
影响因子：
3.7
通讯作者：
Zhu, Xiaotong
中科院分区：
文献类型：
--
作者：
He, Lu;Qiu, Yue;Pang, Geping;Li, Siqi;Wang, Jingjing;Feng, Yonghui;Chen, Lumeng;Zhu, Liying;Liu, Yinjie;Cui, Liwang;Cao, Yaming;Zhu, Xiaotong
疟原虫裂殖子对红细胞的周期性侵入与疟疾的症状和病理学有关。裂殖子的侵入是由一种叫做滑体的寄生虫肌动球蛋白发动机主动而迅速地提供动力的。滑体产生力以支持裂殖子进入宿主RBC的能力被认为依赖于其通过膜驻留蛋白（如GAP 50和GAP 40）在内膜复合物（IMC）内的稳定锚定。使用条件性敲除（KD）方法，我们确定PfGAP 40是无性血液阶段复制所需的。PfGAP 40对于裂殖子从宿主RBC中排出或裂殖子与新RBC的附着是不需要的。PfGAP 40与PfGAP 45和PfGAP 50共沉淀。在裂殖子侵入过程中，PfGAP 40与稳定裂殖子期PfGAP 45和PfGAP 50的表达水平密切相关。虽然PfGAP 40 KD不影响IMC的完整性，但它损害了配子母细胞的成熟。此外，PfGAP 40是磷酸化的，并且阻断PfGAP 40在C末端丝氨酸残基S370、S372、S376、S405、S409、S420和S445处的磷酸化的突变降低裂殖子侵入效率。总体而言，我们的研究结果表明PfGAP 40是裂殖子滑行活性的重要调节因子，并表明PfGAP 40的功能需要磷酸化。红细胞侵入是疟疾寄生虫发病机制的核心，参与这一过程的寄生虫蛋白是潜在的治疗靶点。滑行运动的权力裂殖子入侵，是由一个独特的分子马达称为滑行体。滑动体通过膜驻留蛋白稳定地锚定到寄生虫内膜复合物（IMC）。在本研究中，我们证明了IMC驻留的滑体组分PfGAP 40的重要性，PfGAP 40在稳定滑体组分的表达水平中起着至关重要的作用。我们确定PfGAP 40在C-末端残基的磷酸化是裂殖子有效侵入所必需的。
Cyclic invasion of red blood cells (RBCs) by Plasmodium merozoites is associated with the symptoms and pathology of malaria. Merozoite invasion is powered actively and rapidly by a parasite actomyosin motor called the glideosome. The ability of the glideosome to generate force to support merozoite entry into the host RBCs is thought to rely on its stable anchoring within the inner membrane complex (IMC) through membrane-resident proteins, such as GAP50 and GAP40. Using a conditional knockdown (KD) approach, we determined that PfGAP40 was required for asexual blood-stage replication. PfGAP40 is not needed for merozoite egress from host RBCs or for the attachment of merozoites to new RBCs. PfGAP40 coprecipitates with PfGAP45 and PfGAP50. During merozoite invasion, PfGAP40 is associated strongly with stabilizing the expression levels of PfGAP45 and PfGAP50 in the schizont stage. Although PfGAP40 KD did not influence IMC integrity, it impaired the maturation of gametocytes. In addition, PfGAP40 is phosphorylated, and mutations that block phosphorylation of PfGAP40 at the C-terminal serine residues S370, S372, S376, S405, S409, S420, and S445 reduced merozoite invasion efficiency. Overall, our findings implicate PfGAP40 as an important regulator for the gliding activity of merozoites and suggest that phosphorylation is required for PfGAP40 function. IMPORTANCE Red blood cell invasion is central to the pathogenesis of the malaria parasite, and the parasite proteins involved in this process are potential therapeutic targets. Gliding motility powers merozoite invasion and is driven by a unique molecular motor termed the glideosome. The glideosome is stably anchored to the parasite inner membrane complex (IMC) through membrane-resident proteins. In the present study, we demonstrate the importance of an IMC-resident glideosome component, PfGAP40, that plays a critical role in stabilizing the expression levels of glideosome components in the schizont stage. We determined that phosphorylation of PfGAP40 at C-terminal residues is required for efficient merozoite invasion.
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影响因子：
6.7
作者：
Nebl T;Prieto JH;Kapp E;Smith BJ;Williams MJ;Yates JR 3rd;Cowman AF;Tonkin CJ
通讯作者：
Tonkin CJ
弓形虫的裂解周期：15年后。
影响因子：
10.5
作者：
Blader IJ;Coleman BI;Chen CT;Gubbels MJ
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Gubbels MJ
影响因子：
48
作者：
Andenmatten, Nicole;Egarter, Saskia;Jackson, Allison J;Jullien, Nicolas;Herman, Jean-Paul;Meissner, Markus
通讯作者：
Meissner, Markus
影响因子：
5.6
作者：
Kortagere S;Welsh WJ;Morrisey JM;Daly T;Ejigiri I;Sinnis P;Vaidya AB;Bergman LW
通讯作者：
Bergman LW
影响因子：
3.4
作者：
Douse CH;Vrielink N;Wenlin Z;Cota E;Tate EW
通讯作者：
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