20S proteasomes exported by malaria parasite promote its growth

Mature Red Blood Cells (RBCs) lack internal organelles and canonical defense mechanisms, making them both a fascinating host cell, in general, and an intriguing choice for the deadly malaria parasite Plasmodium falciparum (Pf), in particular. While growing inside RBCs, Pf are known to secrete multipurpose extracellular vesicles (EVs), yet their influence on this parasite’s essential host cell, the RBC, remains unknown. Here we demonstrate that Pf parasites export within such EVs assembled and functional 20S proteasome complexes (EV-20S). The EV-20S proteasomes modulate the mechanical properties of naïve host RBCs by remodeling the cytoskeleton network. Furthermore, we identified four novel degradation targets of the exported 20S proteasome, the phosphorylated cytoskelatal proteins β-adducin, ankyrin-1, dematin and Epb4.1. Overall, our findings reveal a previously unknown 20S proteasome export mechanism of Pf-iRBCs, which prime naïve RBC by altering membrane stiffness, to facilitate malaria parasite growth.