Abstract
Protozoa in the phylum Apicomplexa are a large group of obligate intracellular parasites. Toxoplasma gondii and other apicomplexan parasites, such as Plasmodium falciparum, cause diseases by reiterating their lytic cycle, comprising host cell invasion, parasite replication, and parasite egress. The successful completion of the lytic cycle requires that the parasite senses changes in its environment and switches between the non-motile (for intracellular replication) and motile (for invasion and egress) states appropriately. Although the signaling pathway that regulates the motile state switch is critical to the pathogenesis of the diseases caused by these parasites, it is not well understood. Here we report a previously unknown mechanism of regulating the motility activation in Toxoplasma, mediated by a protein lysine methyltransferase, AKMT (for Apical complex lysine (K) methyltransferase). AKMT depletion greatly inhibits activation of motility, compromises parasite invasion and egress, and thus severely impairs the lytic cycle. Interestingly, AKMT redistributes from the apical complex to the parasite body rapidly in the presence of egress-stimulating signals that increase [Ca2+] in the parasite cytoplasm, suggesting that AKMT regulation of parasite motility might be accomplished by the precise temporal control of its localization in response to environmental changes.
Highlights
Toxoplasma gondii is one of the most successful human parasites, infecting,20% of the total world population
We report a previously unknown mechanism of regulating the motility activation in Toxoplasma, mediated by a novel protein lysine methyltransferase, AKMT (for Apical complex lysine (K) methyltransferase)
The localization of AKMT in the parasite is sensitive to egress-stimulating signals, suggesting that AKMT regulation of parasite motility might be accomplished by the precise temporal control of its localization in response to environmental changes
Summary
Toxoplasma gondii is one of the most successful human parasites, infecting ,20% of the total world population. It belongs to the phylum Apicomplexa, which includes Plasmodium falciparum, the most lethal form of malaria parasites [1]. Its pathogenesis absolutely depends on the parasite’s ability to reiterate its lytic cycle, which is composed of host cell invasion, intracellular replication and egress. T. gondii moves along the host cell surface using actomyosin-based gliding motility, attaches, and rapidly invades, establishing a parasitophorous vacuole in which the parasite replicates [2,3,4,5,6,7] (Figure 1A). The Ca2+ signal prompts several dramatic behavioral changes, including the extension of the cytoskeletal apical complex, a set of apicomplexan-unique cytoskeletal structures at the anterior end of the parasite (Figure 1A); the secretion from micronemes, a membrane-bound organelle; and the stimulation of parasite motility [2,8,9,10,11,12,13,14,15,16]
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