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

Ryan W.J. Steel, Vladimir Vigdorovich, Nicholas Dambrauskas, Brandon K. Wilder, Silvia A. Arredondo, Debashree Goswami, Sudhir Kumar, Sara Carbonetti, Kristian E. Swearingen, Thao Nguyen, Will Betz, Nelly Camargo, Bridget S. Fisher, Jo Soden, Helen Thomas, Jim Freeth, Robert L. Moritz, D. Noah Sather, Stefan H.I. Kappe

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish (US)
Article number11328
JournalScientific Reports
Volume11
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • General

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