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A DOC2 protein identified by mutational profiling is essential for apicomplexan parasite exocytosis.

ABSTRACT: Exocytosis is essential to the lytic cycle of apicomplexan parasites and required for the pathogenesis of toxoplasmosis and malaria. DOC2 proteins recruit the membrane fusion machinery required for exocytosis in a Ca(2+)-dependent fashion. Here, the phenotype of a Toxoplasma gondii conditional mutant impaired in host cell invasion and egress was pinpointed to a defect in secretion of the micronemes, an apicomplexan-specific organelle that contains adhesion proteins. Whole-genome sequencing identified the etiological point mutation in TgDOC2.1. A conditional allele of the orthologous gene engineered into Plasmodium falciparum was also defective in microneme secretion. However, the major effect was on invasion, suggesting that microneme secretion is dispensable for Plasmodium egress.

SUBMITTER: Farrell A

PROVIDER: S-EPMC3354045 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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A DOC2 protein identified by mutational profiling is essential for apicomplexan parasite exocytosis.

Farrell Andrew A Thirugnanam Sivasakthivel S Lorestani Alexander A Dvorin Jeffrey D JD Eidell Keith P KP Ferguson David J P DJ Anderson-White Brooke R BR Duraisingh Manoj T MT Marth Gabor T GT Gubbels Marc-Jan MJ

Science (New York, N.Y.) 20120101 6065

Exocytosis is essential to the lytic cycle of apicomplexan parasites and required for the pathogenesis of toxoplasmosis and malaria. DOC2 proteins recruit the membrane fusion machinery required for exocytosis in a Ca(2+)-dependent fashion. Here, the phenotype of a Toxoplasma gondii conditional mutant impaired in host cell invasion and egress was pinpointed to a defect in secretion of the micronemes, an apicomplexan-specific organelle that contains adhesion proteins. Whole-genome sequencing ident ...[more]

PMID: 22246776

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