Location and function of Plasmodium kinesins: key roles in parasite proliferation, polarity, and transmission

Abstract

AbstractKinesins are microtubule-based motors important in cell division, motility, polarity and intracellular transport in many eukaryotes, but poorly studied in eukaryotic pathogens. Plasmodium spp., the causative agents of malaria, are divergent eukaryotes with atypical aspects of cell division and plasticity of morphology throughout the lifecycle in both mammalian and mosquito hosts. Here we describe a genome-wide screen of 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 and invasive stages of parasite transmission through the mosquito vector. In-depth analyses of kinesin-13 and kinesin-20 revealed functions in microtubule dynamics during apical polarity formation, spindle assembly and axoneme biogenesis. This comprehensive study will inform the targeting of microtubule motors for therapeutic intervention in malaria.