ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
Front Cell Infect Microbiol. 2019 Jul 3;9:238. doi: 10.3389/fcimb.2019.00238. eCollection 2019.
Thrombospondin type I repeat (TSR) domains are commonly -fucosylated by protein -fucosyltransferase 2 (PoFUT2), and this modification is required for optimal folding and secretion of TSR-containing proteins. The human malaria parasite expresses proteins containing TSR domains, such as the thrombospondin-related anonymous protein (TRAP) and circumsporozoite surface protein (CSP), which are -fucosylated. TRAP and CSP are present on the surface of sporozoites and play essential roles in mosquito and human host invasion processes during the transmission stages. Here, we have generated PoFUT2 null-mutant and (rodent) malaria parasites and, by phenotyping them throughout their complete life cycle, we show that PoFUT2 disruption does not affect the growth through the mosquito stages for both species. However, contrary to what has been described previously by others, PoFUT2 null mutant sporozoites showed no deleterious motility phenotypes and successfully established blood stage infection in mice. This unexpected result indicates that the importance of -fucosylation of TSR domains may differ between human and RODENT malaria parasites; complicating our understanding of glycosylation modifications in malaria biology.
血栓反应蛋白 I 型重复（TSR）结构域通常被蛋白岩藻糖基转移酶 2（PoFUT2）-岩藻糖基化，这种修饰对于 TSR 包含蛋白的最佳折叠和分泌是必需的。人类疟原虫表达含有 TSR 结构域的蛋白，如血栓反应蛋白相关的未知蛋白（TRAP）和环子孢子表面蛋白（CSP），这些蛋白都被岩藻糖基化。TRAP 和 CSP 存在于孢子虫的表面，在传播阶段的蚊媒和人体入侵过程中发挥着重要作用。在这里，我们生成了 PoFUT2 缺失突变的 和 （啮齿动物）疟原虫，并通过对它们在整个生命周期中的表型进行研究，我们表明 PoFUT2 缺失突变对这两种疟原虫的蚊媒阶段的生长没有影响。然而，与之前其他人所描述的相反， 缺失突变的孢子虫表现出没有运动表型的缺陷，并且成功地在小鼠中建立了血液阶段感染。这个意外的结果表明，TSR 结构域的岩藻糖基化的重要性可能在人类和啮齿动物疟原虫之间有所不同；这使我们对疟疾生物学中的糖基化修饰的理解变得复杂。
