Platelet derived growth factor receptor β (PDGFRβ) is a host receptor for the human malaria parasite adhesin TRAP
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 prot...
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2021
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oai:doaj.org-article:8c4157eba36149559b9c76a3406ff6532021-12-02T17:50:57ZPlatelet derived growth factor receptor β (PDGFRβ) is a host receptor for the human malaria parasite adhesin TRAP10.1038/s41598-021-90722-52045-2322https://doaj.org/article/8c4157eba36149559b9c76a3406ff6532021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90722-5https://doaj.org/toc/2045-2322Abstract 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.Ryan W. J. SteelVladimir VigdorovichNicholas DambrauskasBrandon K. WilderSilvia A. ArredondoDebashree GoswamiSudhir KumarSara CarbonettiKristian E. SwearingenThao NguyenWill BetzNelly CamargoBridget S. FisherJo SodenHelen ThomasJim FreethRobert L. MoritzD. Noah SatherStefan H. I. KappeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) |
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Medicine R Science Q 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 Platelet derived growth factor receptor β (PDGFRβ) is a host receptor for the human malaria parasite adhesin TRAP |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Ryan W. J. Steel |
| title |
Platelet derived growth factor receptor β (PDGFRβ) is a host receptor for the human malaria parasite adhesin TRAP |
| title_short |
Platelet derived growth factor receptor β (PDGFRβ) is a host receptor for the human malaria parasite adhesin TRAP |
| title_full |
Platelet derived growth factor receptor β (PDGFRβ) is a host receptor for the human malaria parasite adhesin TRAP |
| title_fullStr |
Platelet derived growth factor receptor β (PDGFRβ) is a host receptor for the human malaria parasite adhesin TRAP |
| title_full_unstemmed |
Platelet derived growth factor receptor β (PDGFRβ) is a host receptor for the human malaria parasite adhesin TRAP |
| title_sort |
platelet derived growth factor receptor β (pdgfrβ) is a host receptor for the human malaria parasite adhesin trap |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/8c4157eba36149559b9c76a3406ff653 |
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