Plasmodium falciparum secretory and trafficking pathway

The Plasmodium falciparum secretory and trafficking pathway is a specialized system used by the malaria parasite to transport proteins from its cytoplasm to various internal organelles and into the host erythrocyte. This pathway includes the endoplasmic reticulum (ER), Golgi apparatus, and unique structures such as the apicoplast and the Plasmodium Translocon of Exported Proteins (PTEX) located at the parasitophorous vacuole membrane (PVM) (Deponte, 2012, PMID: 22531113; Elsworth et al., 2014, PMID: 25043010). It is vital for the parasite's ability to remodel the host cell, acquire nutrients, and evade the host immune system by exporting virulence factors like PfEMP1 (Cooke et al., 2004, PMID: 15145198). Key enzymes within this pathway, such as Plasmepsin V, which cleaves the Plasmodium Export Element (PEXEL) motif, are essential for the maturation of exported proteins (Boddey et al., 2010, PMID: 20130577). Drugs targeting this pathway, such as Brefeldin A or experimental Plasmepsin V inhibitors like WEHI-916, disrupt these critical transport processes, leading to parasite death (Sleebs et al., 2014, PMID: 24991914). Given the divergence of some pathway components from human orthologs, it serves as a significant area for the development of novel antimalarials (Heiber et al., 2013, PMID: 23418187).

Other names

Plasmodium falciparum protein export pathwayPlasmodium falciparum endomembrane systemPf secretory pathwayPf trafficking pathway

Inhibition of protein translocation into the endoplasmic reticulum, blockade of PEXEL motif cleavage by Plasmepsin V, disruption of Golgi-mediated vesicle trafficking, or inhibition of the PTEX translocon at the parasitophorous vacuole membrane.