TgCDPK3 Regulates Calcium-Dependent Egress of Toxoplasma gondii from Host Cells
- Author(s)
- Mccoy, JM; Whitehead, L; van Dooren, GG; Tonkin, CJ;
- Details
- Publication Year 2012-12,Volume 8,Issue #12,Page e1003066
- Journal Title
- PLOS PATHOGENS
- Publication Type
- Journal Article
- Abstract
- The phylum Apicomplexa comprises a group of obligate intracellular parasites of broad medical and agricultural significance, including Toxoplasma gondii and the malaria-causing Plasmodium spp. Key to their parasitic lifestyle is the need to egress from an infected cell, actively move through tissue, and reinvade another cell, thus perpetuating infection. Ca2+-mediated signaling events modulate key steps required for host cell egress, invasion and motility, including secretion of microneme organelles and activation of the force-generating actomyosin-based motor. Here we show that a plant-like Calcium-Dependent Protein Kinase (CDPK) in T. gondii, TgCDPK3, which localizes to the inner side of the plasma membrane, is not essential to the parasite but is required for optimal in vitro growth. We demonstrate that TgCDPK3, the orthologue of Plasmodium PfCDPK1, regulates Ca2+ ionophore-and DTT-induced host cell egress, but not motility or invasion. Furthermore, we show that targeting to the inner side of the plasma membrane by dual acylation is required for its activity. Interestingly, TgCDPK3 regulates microneme secretion when parasites are intracellular but not extracellular. Indeed, the requirement for TgCDPK3 is most likely determined by the high K+ concentration of the host cell. Our results therefore suggest that TgCDPK3's role differs from that previously hypothesized, and rather support a model where this kinase plays a role in rapidly responding to Ca2+ signaling in specific ionic environments to upregulate multiple processes required for gliding motility.
- Publisher
- PUBLIC LIBRARY SCIENCE
- Keywords
- PROTEIN-KINASE 1; APICOMPLEXAN PARASITES; GLIDING MOTILITY; PARASITOPHOROUS VACUOLE; MICRONEME DISCHARGE; GENE-EXPRESSION; INVASION; IDENTIFICATION; TRANSMISSION; INHIBITORS
- Research Division(s)
- Infection And Immunity
- Publisher's Version
- https://doi.org/10.1371/journal.ppat.1003066
- Open Access at Publisher's Site
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003066- Terms of Use/Rights Notice
- Copyright: © 2012 McCoy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Creation Date: 2012-12-01 12:00:00