Members of the myosin superfamily are found in all eukaryotes, including Plasmodium falciparum, the parasite that causes the majority of severe malaria. They possess a limited and largely uncharacterised set of unconventional myosins that are distinct in sequence and structure from those of their human host. This evolutionary divergence offers a promising opportunity to exploit P. falciparum myosins as selective drug targets. In this paper, a collaboration between the Buss and Rayner labs, we characterise PfMyoF. This has been shown to function during the asexual blood stage of the P. falciparum life cycle, the stage responsible for the clinical symptoms and mortality associated with malaria.
We show that PfMyoF is a plus-end-directed, processive motor with a long neck region with capacity to bind up to six copies of the calmodulin homologue PfCaM. The PfMyoF tail contains predicted WD40 and Rab-like domains that have not been identified in any other eukaryotic myosin class. Pull-down experiments identify PfMyoF interactions with trafficking proteins, including the vesicle marker PfRab18. Expansion and immunoelectron microscopy reveal that PfMyoF localises to a perinuclear membrane compartment and transient knockdown using the glmS ribozyme system impairs growth. This potentially indicates an important function during asexual replication.
These findings define PfMyoF as the first myosin with a Rab-like domain and highlight its potential role in membrane trafficking pathways during the pathogenic blood stages of parasite development.