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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
- Publication Year :
- 2017
- Publisher :
- American Society for Biochemistry and Molecular Biology, 2017.
-
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 Δcdpk3-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.
- Subjects :
- 0301 basic medicine
030102 biochemistry & molecular biology
Gliding motility
Kinase
Intracellular parasite
Mutant
Calcium-Binding Proteins
Protozoan Proteins
Cell Biology
Biology
Biochemistry
Microbiology
Cell biology
03 medical and health sciences
030104 developmental biology
Lytic cycle
stomatognathic system
Phosphorylation
Calcium Signaling
Signal transduction
Molecular Biology
Protein Kinases
Toxoplasma
Genetic screen
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....57b7e5f92af7f1d759dd269e1edbc0ac