TgCDPK3 regulates calcium-dependent egress of Toxoplasma gondii from host cells.

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,...

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Autores principales:	James M McCoy, Lachlan Whitehead, Giel G van Dooren, Christopher J Tonkin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/faf35d1fec8a42dabecd1e9153a6e54d
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spelling	oai:doaj.org-article:faf35d1fec8a42dabecd1e9153a6e54d2021-11-18T06:06:17ZTgCDPK3 regulates calcium-dependent egress of Toxoplasma gondii from host cells.1553-73661553-737410.1371/journal.ppat.1003066https://doaj.org/article/faf35d1fec8a42dabecd1e9153a6e54d2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23226109/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The 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.James M McCoyLachlan WhiteheadGiel G van DoorenChristopher J TonkinPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 12, p e1003066 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 James M McCoy Lachlan Whitehead Giel G van Dooren Christopher J Tonkin TgCDPK3 regulates calcium-dependent egress of Toxoplasma gondii from host cells.
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 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.
format	article
author	James M McCoy Lachlan Whitehead Giel G van Dooren Christopher J Tonkin
author_facet	James M McCoy Lachlan Whitehead Giel G van Dooren Christopher J Tonkin
author_sort	James M McCoy
title	TgCDPK3 regulates calcium-dependent egress of Toxoplasma gondii from host cells.
title_short	TgCDPK3 regulates calcium-dependent egress of Toxoplasma gondii from host cells.
title_full	TgCDPK3 regulates calcium-dependent egress of Toxoplasma gondii from host cells.
title_fullStr	TgCDPK3 regulates calcium-dependent egress of Toxoplasma gondii from host cells.
title_full_unstemmed	TgCDPK3 regulates calcium-dependent egress of Toxoplasma gondii from host cells.
title_sort	tgcdpk3 regulates calcium-dependent egress of toxoplasma gondii from host cells.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/faf35d1fec8a42dabecd1e9153a6e54d
work_keys_str_mv	AT jamesmmccoy tgcdpk3regulatescalciumdependentegressoftoxoplasmagondiifromhostcells AT lachlanwhitehead tgcdpk3regulatescalciumdependentegressoftoxoplasmagondiifromhostcells AT gielgvandooren tgcdpk3regulatescalciumdependentegressoftoxoplasmagondiifromhostcells AT christopherjtonkin tgcdpk3regulatescalciumdependentegressoftoxoplasmagondiifromhostcells
_version_	1718424580143448064

TgCDPK3 regulates calcium-dependent egress of Toxoplasma gondii from host cells.

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