Abstract
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 mutants 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.
Competing Interest Statement
The authors have declared no competing interest.
The abbreviations used are
- TRAP
- thrombospondin-related anonymous protein;
- VWA
- von Willebrand factor A;
- MIDAS
- metal ion-dependent adhesion site;
- TSR
- thrombospondin repeat;
- HSPGs
- heparan sulfate proteoglycans;
- hPDGFRβ
- human platelet-derived growth factor receptor β;
- gMFI
- geometric mean fluorescence intensity.