Adhesion of IEs is mediated by members of the highly polymorphic and clonally variant P. falciparum erythrocyte membrane protein 1 (PfEMP1) encoded by the var gene family. We have previously shown that CM is associated to IEs binding to the endothelial receptors ICAM-1 and EPCR and that PM is associated to IEs binding to placental chondroitin sulfate A (CSA) via PfEMP1-VAR2CSA. Our team is currently decrypting these interactions, notably identifying interacting partners associated with PfEMP1 trafficking and IEs surface display, to dissect their respective contribution in parasite biology and pathogenicity.
We have recently shown that VAR2CSA is phosphorylated and that the phosphorylation plays a major role in VAR2CSA interaction with CSA. Although VAR2CSA interaction with CSA is well described, interactions between VAR2CSA and host or other parasite proteins are poorly understood. Our working hypothesis is that different types of post-translational modifications (PTM) could modulate or control parasite trafficking and cytoadhesion to host receptors, and that plasma components and parasite molecules could interact with PfEMP1 to modulate cytoadhesion. We will perform a comprehensive analysis of PTM that modulate PfEMP1 function, and identify the interacting partners associated with PfEMP1 trafficking and IEs surface display to dissect their contribution in the parasite biology and pathology.