Genome-wide localisation and function analysis of Plasmodium kinesins: key roles in proliferation, polarity and transmission

Kinesins are microtubule-based motors functional in cell division, motility, polarity and intracellular transport in many eukaryotes, but poorly studied in eukaryotic pathogens. Plasmodium, the causative agent of malaria, is a divergent eukaryote with atypical aspects of cell division and a plasticity of morphology throughout its lifecycle in both mammalian and mosquito hosts. Here we describe a genome-wide screen of all nine Plasmodium kinesins, revealing diverse subcellular locations and functions in spindle assembly, axoneme formation and cell morphology. Surprisingly, only kinesin-13 has an essential role for growth in the mammalian host while the other eight kinesins are required during the proliferative andinvasive stages of parasite transmission through the mosquito vector. In-depth analyses of kinesin-13 and kinesin-20 revealed functions in microtubule (MT) dynamics during apical polarity formation, spindle assembly and axoneme biogenesis. This comprehensive study will inform the targeting of MT motors for therapeutic intervention in malaria.