TgCDPK3 Regulates Calcium-Dependent Egress of Toxoplasma gondii from Host Cells
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McCoy, James M.; Whitehead, Lachlan; van Dooren, Giel G.; Tonkin, Christopher J.
Description
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. Ca(2+)-mediated signaling events modulate key steps required for host cell egress, invasion and motility, including secretion of microneme...[Show more]
dc.contributor.author | McCoy, James M. | |
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dc.contributor.author | Whitehead, Lachlan | |
dc.contributor.author | van Dooren, Giel G. | |
dc.contributor.author | Tonkin, Christopher J. | |
dc.date.accessioned | 2015-11-26T04:05:28Z | |
dc.date.available | 2015-11-26T04:05:28Z | |
dc.identifier.issn | 1553-7374 | |
dc.identifier.uri | http://hdl.handle.net/1885/16836 | |
dc.description.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. Ca(2+)-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 Ca(2+) 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 Ca(2+) signaling in specific ionic environments to upregulate multiple processes required for gliding motility. | |
dc.description.sponsorship | This work was supported by the National Health and Medical Research Council (NHMRC) Project Grant APP1025598. JMM is supported by a Australian Postgraduate Award, GGvD is supported by an Australian Research Council QEII Fellowship and CJT is supported by an NHMRC Career Development Award. This work was also made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | |
dc.publisher | Public Library of Science | |
dc.rights | © 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. | |
dc.source | PLoS Pathogens | |
dc.source.uri | http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003066 | |
dc.subject | animals | |
dc.subject | calcium | |
dc.subject | cell line | |
dc.subject | humans | |
dc.subject | protein kinases | |
dc.subject | protozoan proteins | |
dc.subject | rabbits | |
dc.subject | toxoplasma | |
dc.subject | toxoplasmosis | |
dc.subject | calcium signaling | |
dc.subject | host-pathogen interactions | |
dc.title | TgCDPK3 Regulates Calcium-Dependent Egress of Toxoplasma gondii from Host Cells | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 8 | |
dc.date.issued | 2012-12-04 | |
local.identifier.absfor | 060500 | |
local.identifier.ariespublication | f5625xPUB2300 | |
local.publisher.url | http://journals.plos.org/ | |
local.type.status | Published Version | |
local.contributor.affiliation | McCoy, James M, The Walter and Eliza Hall Institute of Medical Research, Australia | |
local.contributor.affiliation | Whitehead, Lachlan, The Walter and Eliza Hall Institute of Medical Research, Australia | |
local.contributor.affiliation | van Dooren, Giel, College of Medicine, Biology and Environment, CMBE Research School of Biology, Division of Biomedical Science and Biochemistry, The Australian National University | |
local.contributor.affiliation | Tonkin, Christopher J, The Walter and Eliza Hall Institute of Medical Research, Australia | |
dc.relation | http://purl.org/au-research/grants/nhmrc/1025598 | |
local.identifier.essn | 1553-7374 | |
local.bibliographicCitation.issue | 12 | |
local.bibliographicCitation.startpage | e1003066 | |
local.identifier.doi | 10.1371/journal.ppat.1003066 | |
dc.date.updated | 2015-12-10T11:58:25Z | |
local.identifier.scopusID | 2-s2.0-84872010969 | |
local.identifier.thomsonID | 000312907100021 | |
Collections | ANU Research Publications |
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