Platelet derived growth factor receptor β (PDGFRβ) is a host receptor for the human malaria parasite adhesin TRAP.

Platelet derived growth factor receptor β (PDGFRβ) is a host receptor for the human malaria parasite adhesin TRAP.
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DOI:
10.1038/s41598-021-90722-5
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发表时间:
2021-05-31
期刊:
影响因子:
4.6
通讯作者:
Kappe SHI
Kappe SHI
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Steel RWJ;Vigdorovich V;Dambrauskas N;Wilder BK;Arredondo SA;Goswami D;Kumar S;Carbonetti S;Swearingen KE;Nguyen T;Betz W;Camargo N;Fisher BS;Soden J;Thomas H;Freeth J;Moritz RL;Noah Sather D;Kappe SHI

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在被感染的按蚊叮咬接种后,疟疾寄生虫子孢子从皮肤的叮咬部位进入血液,再将它们输送到肝脏。凝血酶敏感蛋白相关匿名蛋白(TRAP)是一种由分泌细胞器释放并重新定位于子孢子质膜的1型跨膜蛋白。TRAP是子孢子运动和宿主感染所必需的,其胞外部分含有预测与宿主受体结合的粘附域。在此,我们鉴定了人血小板衍生生长因子受体β(hPDGFRβ)就是一种这样的蛋白受体。缺失构建表明,与hPDGFRβ表达细胞的最佳结合都需要TRAP的von Willebrand因子A型和凝血酶反应蛋白重复结构域。我们还证明了这种相互作用在人感染的间日疟原虫中是保守的,但在啮齿动物感染的寄生虫约氏疟原虫中不是。我们观察到hPDGFRβ主要在与血管系统相关的细胞中表达,提示TRAP:hPDGFRβ相互作用可能在侵袭子孢子识别血管中发挥作用。
Following their inoculation by the bite of an infected Anopheles mosquito, the malaria parasite sporozoite forms travel from the bite site in the skin into the bloodstream, which transports them to the liver. The thrombospondin-related anonymous protein (TRAP) is a type 1 transmembrane protein that is released from secretory organelles and relocalized on the sporozoite plasma membrane. TRAP is required for sporozoite motility and host infection, and its extracellular portion contains adhesive domains that are predicted to engage host receptors. Here, we identified the human platelet-derived growth factor receptor β (hPDGFRβ) as one such protein receptor. Deletion constructs showed that the von Willebrand factor type A and thrombospondin repeat domains of TRAP are both required for optimal binding to hPDGFRβ-expressing cells. We also demonstrate that this interaction is conserved in the human-infective parasite Plasmodium vivax, but not the rodent-infective parasite Plasmodium yoelii. We observed expression of hPDGFRβ mainly in cells associated with the vasculature suggesting that TRAP:hPDGFRβ interaction may play a role in the recognition of blood vessels by invading sporozoites.
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