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A forward genetic screen identifies a negative regulator of rapid Ca2+-dependent cell egress (MS1) in the intracellular parasite Toxoplasma gondii.


ABSTRACT: Toxoplasma gondii, like all apicomplexan parasites, uses Ca2+ signaling pathways to activate gliding motility to power tissue dissemination and host cell invasion and egress. A group of "plant-like" Ca2+-dependent protein kinases (CDPKs) transduces cytosolic Ca2+ flux into enzymatic activity, but how they function is poorly understood. To investigate how Ca2+ signaling activates egress through CDPKs, we performed a forward genetic screen to isolate gain-of-function mutants from an egress-deficient cdpk3 knockout strain. We recovered mutants that regained the ability to egress from host cells that harbored mutations in the gene Suppressor of Ca2+-dependent Egress 1 (SCE1). Global phosphoproteomic analysis showed that SCE1 deletion restored many ?cdpk3-dependent phosphorylation events to near wild-type levels. We also show that CDPK3-dependent SCE1 phosphorylation is required to relieve its suppressive activity to potentiate egress. In summary, our work has uncovered a novel component and suppressor of Ca2+-dependent cell egress during Toxoplasma lytic growth.

SUBMITTER: McCoy JM 

PROVIDER: S-EPMC5418062 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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A forward genetic screen identifies a negative regulator of rapid Ca<sup>2+</sup>-dependent cell egress (MS1) in the intracellular parasite <i>Toxoplasma gondii</i>.

McCoy James M JM   Stewart Rebecca J RJ   Uboldi Alessandro D AD   Li Dongdi D   Schröder Jan J   Scott Nicollas E NE   Papenfuss Anthony T AT   Lehane Adele M AM   Foster Leonard J LJ   Tonkin Christopher J CJ  

The Journal of biological chemistry 20170303 18


<i>Toxoplasma gondii</i>, like all apicomplexan parasites, uses Ca<sup>2+</sup> signaling pathways to activate gliding motility to power tissue dissemination and host cell invasion and egress. A group of "plant-like" Ca<sup>2+</sup>-dependent protein kinases (CDPKs) transduces cytosolic Ca<sup>2+</sup> flux into enzymatic activity, but how they function is poorly understood. To investigate how Ca<sup>2+</sup> signaling activates egress through CDPKs, we performed a forward genetic screen to isol  ...[more]

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