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

• Published in: Scientific reports 2021-05, Vol.11 (1), p.11328-11328, Article 11328
• Main Authors: Steel, Ryan W. J., Vigdorovich, Vladimir, Dambrauskas, Nicholas, Wilder, Brandon K., Arredondo, Silvia A., Goswami, Debashree, Kumar, Sudhir, Carbonetti, Sara, Swearingen, Kristian E., Nguyen, Thao, Betz, Will, Camargo, Nelly, Fisher, Bridget S., Soden, Jo, Thomas, Helen, Freeth, Jim, Moritz, Robert L., Noah Sather, D., Kappe, Stefan H. I.
• Format: Article
• Language: English
• Subjects: 631/326/417; 631/45/612; 692/420/254; Blood vessels; Erythrocytes; Growth factors; HEK293 Cells; Host-Pathogen Interactions; Humanities and Social Sciences; Humans; Inoculation; Malaria; multidisciplinary; Organelles; Parasites; Plasmodium falciparum - metabolism; Plasmodium vivax - metabolism; Plasmodium yoelii - metabolism; Platelet-derived growth factor; Proteins; Protozoan Proteins - isolation & purification; Protozoan Proteins - metabolism; Receptor, Platelet-Derived Growth Factor beta - metabolism; Science; Science (multidisciplinary); Sporozoites; Thrombospondin; Thrombospondin-related anonymous protein; Vector-borne diseases; Von Willebrand factor
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-90722-5

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.