The Motility of a Human Parasite, Toxoplasma gondii, Is Regulated by a Novel Lysine Methyltransferase

PLoS Pathogens

Aoife T. Heaslip¹  Manami Nishi¹  Ke Hu¹  Barry Stein¹ 

[1] Department of Biology, Indiana University, Bloomington, Indiana, United States of America

关键词: Parasite replication;    Parasitic diseases;    Host cells;    Lysine;    Toxoplasma gondii;    Vacuoles;    Pathogen motility;    Histones;   

DOI  :  10.1371/journal.ppat.1002201

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY