Interaction of Plasmodium falciparum casein kinase 1 with components of host cell protein trafficking machinery.

A pool of Plasmodium falciparum casein kinase 1 (PfCK1) has been shown to localize to the host red blood cell (RBC) membrane and be secreted to the extracellular medium during trophozoite stage of development. We attempted to identify mechanisms for secretion of PfCK1 and its appearance on the RBC membrane. We found that two host proteins with established functions in membrane trafficking in higher eukaryotes, GTPase-activating protein and Vps9 domain-containing protein 1 (GAPVD1), and Sorting nexin 22, consistently co-purify with PfCK1, suggesting that the parasite utilizes trafficking pathways previously thought to be inactive in RBCs. Furthermore, reciprocal immunoprecipitation experiments with GAPVD1 identified parasite proteins suggestive of a protein recycling pathway hitherto only described in higher eukaryotes. Thus, we have identified components of a trafficking pathway involving parasite proteins that act in concert with host proteins, and which we hypothesize mediates trafficking of PfCK1 to the RBC during infection.