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

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 beta (hPDGFR beta) 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 hPDGFR beta -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 hPDGFR beta mainly in cells associated with the vasculature suggesting that TRAP:hPDGFR beta interaction may play a role in the recognition of blood vessels by invading sporozoites.

Automated summary

Following inoculation by an infected mosquito, the malaria parasite travels to the liver through the bloodstream. The protein TRAP plays a crucial role in sporozoite motility and infection, and interacts with the human platelet-derived growth factor receptor beta. This interaction is conserved in human-infective Plasmodium vivax, suggesting a role in sporozoite recognition of blood vessels.