A DOC2 Protein Identified by Mutational Profiling Is Essential for Apicomplexan Parasite Exocytosis

Author:

Farrell Andrew1,Thirugnanam Sivasakthivel1,Lorestani Alexander1,Dvorin Jeffrey D.23,Eidell Keith P.1,Ferguson David J.P.4,Anderson-White Brooke R.1,Duraisingh Manoj T.2,Marth Gabor T.1,Gubbels Marc-Jan1

Affiliation:

1. Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.

2. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.

3. Division of Infectious Diseases, Children’s Hospital Boston, Boston, MA 02115, USA.

4. Nuffield Department of Clinical Laboratory Science, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.

Abstract

Parasite Invasion Strategy Exocytosis is essential to the lytic cycle of apicomplexan parasites and is required for the pathogenesis of toxoplasmosis and malaria. DOC2 proteins recruit the membrane fusion machinery required for exocytosis in a Ca 2+ -dependent fashion. Farrell et al. (p. 218 ) describe the phenotype of a Toxoplasma gondii conditional mutant impaired in host cell invasion and egress. The phenotype was explained by a defect in secretion of the micronemes, an apicomplexan-specific organelle that contains adhesion proteins. A T. gondii Doc2 gene was identified, by whole-genome sequencing, to be involved in the secretion defect, and a conditional allele of the orthologous gene engineered into the malaria parasite, Plasmodium falciparum , also caused defects in microneme secretion.

Funder

National Institutes of Health

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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