Thursday, October 27, 2016

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

 2016 Oct 26. doi: 10.1111/cmi.12685. [Epub ahead of print]


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+ signalling 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+ signalling 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+ signalling 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.

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