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Paper published by the CIDR explores novel receptor interaction with human malaria parasite TRAP

Platelet Derived Growth Factor Receptor β (PDGFRβ) is a Host Receptor for the human malaria parasite adhesin TRAP

Malaria is a life-threatening disease, initiated from a bite of an infected Anopheles mosquito. Sporozoites are injected into the skin, which work their way to blood vessels, using unknown host interactions, and eventually being transported to the liver. A recent paper published in Scientific Reports demonstrates the value of the Retrogenix cell microarray platform in uncovering such molecular interactions.

Thrombospondin-related anonymous protein (TRAP), a type 1 transmembrane protein localised on the sporozoite plasma membrane, has been predicted to engage previously unknown host receptors and facilitate host infection.

A study published by Steel et al., aimed to determine the host receptor for TRAP to better understand the mechanisms facilitating parasitic infection.

Using the Retrogenix cell microarray technology, TRAP was screened against a vast library of plasma membrane proteins, identifying a novel interaction: platelet-derived growth factor receptor beta (PDGFRβ). Further work identified that von Willebrand factor type A and thrombospondin repeat domains of TRAP are both required for optimal binding to hPDGFRβ-expressing cells.

As hPDGFRβ is expressed mainly in cells associated with the vasculature, the identified TRAP:PDGFRβ interaction suggests that this may play a role in the recognition of blood vessels by invading sporozoites. They are then able to move to the liver and differentiate before infecting red blood cells and causing the characteristic clinical symptoms of malaria. This finding contributes to a wider understanding of early infection pathways, facilitating early treatment interventions for malaria, responsible for 400,000 deaths in 2019 (WHO, 2019).

The research was led by scientists at Seattle Children’s Research Institute in collaboration with Retrogenix, the Institute for Systems Biology, and the Department of Pediatrics and Department of Global Health at the University of Washington.

The unique library of Retrogenix, recently acquired by Charles River Laboratories, now contains over 6,200 human plasma membrane and secreted proteins. If you’d like to understand how Retrogenix can uncover the primary receptor and/or off-target(s) of your protein or therapeutic, please contact us.

 

The paper, published by the Center for Infectious Disease Research, Seattle, is entitled: “Platelet Derived Growth Factor Receptor β (PDGFRβ) is a Host Receptor for the human malaria parasite adhesin TRAP.”

Link to the full paper