Analysis of Ca2+ mediated signaling regulating Toxoplasma infectivity reveals complex relationships between key molecules

Host cell invasion, exit and parasite dissemination is critical to the pathogenesis of apicomplexan parasites such as Toxoplasma gondii and Plasmodium spp. These processes are regulated by intracellular Ca2+ signaling although the temporal dynamics of Ca2+ fluxes and down‐stream second messenger pat...

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Published inCellular microbiology Vol. 19; no. 4
Main Authors Stewart, Rebecca J., Whitehead, Lachlan, Nijagal, Brunda, Sleebs, Brad E., Lessene, Guillaume, McConville, Malcolm J., Rogers, Kelly L., Tonkin, Christopher J.
Format Journal Article
LanguageEnglish
Published Oxford Hindawi Limited 01.04.2017
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Abstract Host cell invasion, exit and parasite dissemination is critical to the pathogenesis of apicomplexan parasites such as Toxoplasma gondii and Plasmodium spp. These processes are regulated by intracellular Ca2+ signaling although the temporal dynamics of Ca2+ fluxes and down‐stream second messenger pathways are poorly understood. Here, we use a genetically encoded biosensor, GFP‐Calmodulin‐M13–6 (GCaMP6), to capture Ca2+ flux in live Toxoplasma and investigate the role of Ca2+ signaling in egress and motility. Our analysis determines how environmental cues and signal activation influence intracellular Ca2+ flux, allowing placement of effector molecules within this pathway. Importantly, we have identified key interrelationships between cGMP and Ca2+ signaling that are required for activation of egress and motility. Furthermore, we extend this analysis to show that the Ca2+ Dependent Protein Kinases–TgCDPK1 and TgCDPK3—play a role in signal quenching before egress. This work highlights the interrelationships of second messenger pathways of Toxoplasma in space and time, which is likely required for pathogenesis of all apicomplexan species.
AbstractList Host cell invasion, exit and parasite dissemination is critical to the pathogenesis of apicomplexan parasites such as Toxoplasma gondii and Plasmodium spp. These processes are regulated by intracellular Ca2+ signaling although the temporal dynamics of Ca2+ fluxes and down‐stream second messenger pathways are poorly understood. Here, we use a genetically encoded biosensor, GFP‐Calmodulin‐M13–6 (GCaMP6), to capture Ca2+ flux in live Toxoplasma and investigate the role of Ca2+ signaling in egress and motility. Our analysis determines how environmental cues and signal activation influence intracellular Ca2+ flux, allowing placement of effector molecules within this pathway. Importantly, we have identified key interrelationships between cGMP and Ca2+ signaling that are required for activation of egress and motility. Furthermore, we extend this analysis to show that the Ca2+ Dependent Protein Kinases–TgCDPK1 and TgCDPK3—play a role in signal quenching before egress. This work highlights the interrelationships of second messenger pathways of Toxoplasma in space and time, which is likely required for pathogenesis of all apicomplexan species.
Author Stewart, Rebecca J.
Tonkin, Christopher J.
McConville, Malcolm J.
Rogers, Kelly L.
Whitehead, Lachlan
Lessene, Guillaume
Nijagal, Brunda
Sleebs, Brad E.
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Snippet Host cell invasion, exit and parasite dissemination is critical to the pathogenesis of apicomplexan parasites such as Toxoplasma gondii and Plasmodium spp....
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SubjectTerms Biosensors
Calcium (intracellular)
Calcium ions
Calcium signalling
Calcium-binding protein
Calmodulin
Cyclic GMP
Egress
Fluxes
Genetic code
Infectivity
Intracellular
Intracellular signalling
Kinases
Motility
Parasites
Pathogenesis
Protein kinase
Signal transduction
Signaling
Title Analysis of Ca2+ mediated signaling regulating Toxoplasma infectivity reveals complex relationships between key molecules
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