ANU Open Research Repository has been upgraded. We are still working on a few minor issues, which may result in short outages throughout the day. Please get in touch with repository.admin@anu.edu.au if you experience any issues.
 

TgCDPK3 Regulates Calcium-Dependent Egress of Toxoplasma gondii from Host Cells

Date

2012-12-04

Authors

McCoy, James M.
Whitehead, Lachlan
van Dooren, Giel G.
Tonkin, Christopher J.

Journal Title

Journal ISSN

Volume Title

Publisher

Public Library of Science

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.

Description

Keywords

animals, calcium, cell line, humans, protein kinases, protozoan proteins, rabbits, toxoplasma, toxoplasmosis, calcium signaling, host-pathogen interactions

Citation

Source

PLoS Pathogens

Type

Journal article

Book Title

Entity type

Access Statement

License Rights

DOI

10.1371/journal.ppat.1003066

Restricted until