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

Content Provider	PubMed Central
Author	Mccoy, James M. Whitehead, Lachlan Dooren, Giel G. Van Tonkin, Christopher J.
Editor	Dominique, Soldati-favre
Copyright Year	2012
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.
Related Links	http://dx.doi.org/10.1371/journal.ppat.1003066
Starting Page	1003066
File Format	PDF
ISSN	15537374
e-ISSN	15537374
Journal	PLoS Pathogens
Issue Number	12
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2012-12-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Immunology Genetics Molecular Biology Microbiology Parasitology Virology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Virology Molecular Biology Parasitology Immunology Microbiology

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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Correction: TgCDPK3 Regulates Calcium-Dependent Egress of Toxoplasma gondii from Host Cells

Phosphorylation of a Myosin Motor by TgCDPK3 Facilitates Rapid Initiation of Motility during Toxoplasma gondii egress

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

Phosphorylation of a Myosin Motor by TgCDPK3 Facilitates Rapid Initiation of Motility during Toxoplasma gondii egress

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