Toxoplasma gondii: Calcium lonophore A23187-mediated exit of trophozoites from infected murine macrophages

Endo, Tokiko; Sethi, K. K.; Piekarski, G.

doi:10.1016/0014-4894(82)90059-5

Cited by 131 publications

(108 citation statements)

References 7 publications

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“…3B), after which the integrity of the monolayer declined (data not shown). Previous studies have implicated calcium signaling in parasite egress from infected cells 13, 14 and the rapid increase in ABA concentrations in the parasite just prior to egress (Fig. 2D), suggested this molecule may be the natural signal for activating exit.…”

mentioning

confidence: 69%

Abscisic acid controls calcium-dependent egress and development in Toxoplasma gondii

Nagamune

Hicks

Fux

et al. 2008

Nature

190

174

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Calcium controls a number of critical events including motility, secretion, cell invasion, and egress by protozoan parasites 1. Compared to animal 2 and plant cells 3 , the molecular mechanisms that govern calcium signaling in parasites are poorly understood. Here we demonstrate that the production of the phytohormone abscisic acid (ABA) controls calcium signaling within the apicomplexan parasite Toxoplasma gondii, an important human pathogen. In plants, ABA controls a number of important events including environmental stress responses, embryo development, and seed dormancy 4 ,5 . ABA induces production of the second-messenger cyclic ADP ribose (cADPR), which controls release of intracellular calcium stores in plants 6 . cADPR also controls intracellular calcium release in the protozoan parasite T. gondii 7,8 ; however, previous studies have not revealed the molecular basis of this pathway 9 . Addition of exogenous ABA induced formation of cADPR in T. gondii, stimulated calcium-dependent protein secretion, and induced parasite egress from the infected host cell in a density-dependent manner. Production of endogenous ABA within the parasite was confirmed by HPLC purification and GC-MS analysis. Selective disruption of ABA synthesis by the inhibitor fluridone (FLU) delayed egress and induced development of the slow-growing, dormant cyst stage of the parasite. Thus, ABA-mediated calcium signaling controls the decision between lytic and chronic stage growth, a developmental switch that is central in pathogenesis and transmission. The pathway for ABA production was likely acquired with an algal endosymbiont that was retained as a non-photosynthetic plastid known as the apicoplast. The plant-like nature of this pathway may be exploited therapeutically as shown by the ability of a specific inhibitor of ABA synthesis to prevent toxoplasmosis in the mouse model.Calcium-mediated secretion in T. gondii controls both motility and cell invasion and previous studies have demonstrated that these processes utilize the second messenger cADPR, yet the signals triggering this pathway remain unresolved 7,8 . In plants 6 , hydra 10 , and sponges 11 , ABA stimulates release of intracellular calcium through elevation of the cyclic nucleotide cADPR. Addition of exogenous ABA proved to be a potent agonist of secretion in T. gondii as shown by the release of the protein MIC2, a parasite adhesin that is discharged into the supernatant in response to increases in intracellular calcium (Fig. 1A). Induction of MIC2 secretion by ABA was highly specific to (±) -ABA and was not induced by (−) -ABA, the precursor β-carotene, or retinoic acid (Fig. 1B). Treatment with ABA lead to a dose-dependent increase in the second messenger cADPR in T. gondii, suggesting ABA may be a natural agonist for calcium signaling in parasites (Fig. 1C). Finally, chelation of intracellular calcium in the parasite blocked secretion induced by ABA, confirming that it acts through release of an intracellular calcium pool (Fig. 1D). Collectively these results ind...

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mentioning

confidence: 69%

Abscisic acid controls calcium-dependent egress and development in Toxoplasma gondii

Nagamune

Hicks

Fux

et al. 2008

Nature

190

174

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“…Attempts to use digitonin or saponin were not successful as no conditions could be identified that resulted reproducibly in the permeabilization of the host plasma membrane without affecting the parasite. (9) found that treatment of Toxoplasma-infected host cells with the calcium ionophore A23187 results in a rapid induction of parasite egress. To establish whether increases in host cell [Ca 2ϩ ] C were also involved in the normal, uninduced, egress process, we loaded Toxoplasma-infected cells with the calcium indicator fura-PE3/AM.…”

mentioning

confidence: 99%

“…Thus far, the only clues to the mechanism used by Toxoplasma to regulate its egress from infected cells have come from observations made with two compounds that induce this process artificially. Calcium ionophores, such as A23187, have been found to be effective inducers of Toxoplasma egress (9), suggesting that alterations in the concentration of calcium in either the host cell or the parasite are involved in inducing parasite egress. Recently, Toxoplasma mutants have been isolated that display a delayed response to ionophore-induced parasite egress (10).…”

mentioning

confidence: 99%

The Loss of Cytoplasmic Potassium upon Host Cell Breakdown Triggers Egress of Toxoplasma gondii

Moudy¹,

Manning²,

Beckers³

2001

Journal of Biological Chemistry

182

203

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“…The discharge of microneme proteins leads to the establishment of a bridge between the extracellular matrix or host cell receptors and the glideosome, hence allowing the parasite to move onto the substrate. In T. gondii, microneme secretion can be artificially triggered by ethanol or calcium ionophores Endo et al, 1982;Wetzel et al, 2004). During gliding motility cytosolic calcium levels undergo fast and dramatic changes that reflect multiple sequential microneme discharge events.…”

Section: Microneme Secretion and Egressmentioning

confidence: 99%

Does protein phosphorylation govern host cell entry and egress by the Apicomplexa?

Jacot

Soldati‐Favre

2012

International Journal of Medical Microbiology

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a b s t r a c tMembers of the phylum Apicomplexa are responsible for a wide range of diseases in humans and animals. The absence of an effective vaccine or safe curing drugs and the continuous emergence of resistant parasites to available treatments impose a high demand on the identification of novel targets for intervention against the apicomplexans. Protein kinases are considered attractive potential therapeutic targets not only against cancers but also to combat infectious diseases. The scope and aim of this review is to report on the recent progress in dissecting the impact of protein phosphorylation in regulating motility and invasion.

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Toxoplasma gondii: Calcium lonophore A23187-mediated exit of trophozoites from infected murine macrophages

Cited by 131 publications

References 7 publications

Abscisic acid controls calcium-dependent egress and development in Toxoplasma gondii

Abscisic acid controls calcium-dependent egress and development in Toxoplasma gondii

The Loss of Cytoplasmic Potassium upon Host Cell Breakdown Triggers Egress of Toxoplasma gondii

Does protein phosphorylation govern host cell entry and egress by the Apicomplexa?

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