Phosphatidylinositol 3-Monophosphate Is Involved in Toxoplasma Apicoplast Biogenesis

PLoS Pathogens

Markus Meissner¹  Gaëtan Chicanne²  Bernard Payrastre²  Véronique Richard³  Christian Roy⁴  Maryse Lebrun⁴  Henri J. Vial⁴  Lina Tawk⁴  Kai Wengelnik⁴  Jean-François Dubremetz⁴  Philippe Montcourrier⁵  Fabrice Merezegue⁵ 

[1] Faculty of Biomedical & Life Sciences, Parasitology, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom;INSERM U563, Université Toulouse III Paul-Sabatier, CHU Toulouse, Hôpital Purpan, Toulouse, France;Service Commun de Microscopie Electronique, Université de Montpellier 1 & 2, Montpellier, France;UMR 5235 CNRS, Université Montpellier 1 & 2, Montpellier, France;UMR 5237 CNRS, Université Montpellier 1 & 2, Montpellier, France

关键词: Vesicles;    Toxoplasma gondii;    Cell membranes;    Parasitic diseases;    Vacuoles;    Cellular structures;    organelles;    Tachyzoites;    Membrane trafficking;   

DOI  :  10.1371/journal.ppat.1001286

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Apicomplexan parasites cause devastating diseases including malaria and toxoplasmosis. They harbour a plastid-like, non-photosynthetic organelle of algal origin, the apicoplast, which fulfils critical functions for parasite survival. Because of its essential and original metabolic pathways, the apicoplast has become a target for the development of new anti-apicomplexan drugs. Here we show that the lipid phosphatidylinositol 3-monophosphate (PI3P) is involved in apicoplast biogenesis in Toxoplasma gondii. In yeast and mammalian cells, PI3P is concentrated on early endosomes and regulates trafficking of endosomal compartments. Imaging of PI3P in T. gondii showed that the lipid was associated with the apicoplast and apicoplast protein-shuttling vesicles. Interference with regular PI3P function by over-expression of a PI3P specific binding module in the parasite led to the accumulation of vesicles containing apicoplast peripheral membrane proteins around the apicoplast and, ultimately, to the loss of the organelle. Accordingly, inhibition of the PI3P-synthesising kinase interfered with apicoplast biogenesis. These findings point to an unexpected implication for this ubiquitous lipid and open new perspectives on how nuclear encoded proteins traffic to the apicoplast. This study also highlights the possibility of developing specific pharmacological inhibitors of the parasite PI3-kinase as novel anti-apicomplexan drugs.

【 授权许可】

CC BY