Trafficking

Protein trafficking to the apicoplast in Apicomplexans

Apicomplexa are obligate endo-parasitic pathogens that harbor two organelles of endosymbiotic origin: a mitochondrion (primary endosymbiont) and a relict plastid, the apicoplast (secondary endosymbiont). Trafficking to an unusual endosymbiotic organelle called the apicoplast is under study due to the observations that this organelle is a secondary endosymbiont (thought to be derived from a eukaryotic red algal origin). Further, the organelle is essential for Apicomplexan parasite viability, making it a potential drug target.

Although common in plants, very few proteins are currently known to be localized to both the secondary plastid and the mitochondrion in apicomplexans. One such protein in P. falciparum is glutathione peroxidase-like thioredoxin peroxidase (PfTPxGl) which we show, by immunofluorescence imaging and bioinformatics predictions, to be localized in the apicoplast, the mitochondrion and the cytosol. To study if the mechanism and trafficking pathway of dually targeted proteins is indeed conserved across species, our lab also studies the trafficking of proteins to the apicoplast of Toxoplasma gondii. Amongst these is Thioredoxin peroxidase (TgTPx1/2), the homologue of PfTPxGl in T. gondii. TgTPx1/2 like its homologue in P. falciparum is dually targeted to the apicoplast and mitochondrion. We showed that this protein, and two other proteins that are dually targeted to the apicoplast and mitochondrion, use a Golgi-dependent route for trafficking to the apicoplast. In contrast, exclusive apicoplast proteins use a Golgi-independent route to reach their destination. We have also shown that targeting signals for these two pathways are found throughout the protein, not restricted to the N-terminus.

Our lab is now also focusing on understanding the mechanism of this transport and the proteins involved in trafficking to the apicoplast.

Funded by: Board for Research in Nuclear Sciences (2013/37B/18/BRNS) and Department of Biotechnology (BT/PR13546/BRB/10/1423/2015)

Apicoplast trafficking team