Lipid kinases are essential for apicoplast homeostasis in Toxoplasma gondii

Cell Microbiol. 2014 Oct 20. doi: 10.1111/cmi.12383. [Epub ahead of print]

 

Daher W¹, Morlon-Guyot J, Sheiner L, Lentini G, Berry L, Tawk L, Dubremetz JF, Wengelnik K, Striepen B, Lebrun M.

 

Phosphoinositides regulate numerous cellular processes, by recruiting cytosolic effector proteins and acting as membrane signaling entities. The cellular metabolism and localization of phosphoinositides are tightly regulated by distinct lipid kinases and phosphatases. Here, we identify and characterize a unique phosphatidylinositol 3-Kinase (PI3K) in Toxoplasma gondii, a protozoan parasite belonging to the phylum Apicomplexa. Conditional depletion of this enzyme and subsequently of its product, PI(3)P, drastically alters the morphology and inheritance of the apicoplast, an endosymbiontic organelle of algal origin that is a unique feature of many Apicomplexa. We searched the T. gondii genome for PI(3)P binding proteins and identified in total six PX and FYVE-domain containing proteins including a PIKfyve lipid kinase, which phosphorylates PI(3)P into PI(3,5)P₂ . While depletion of putative PI(3)P binding proteins shows that they are not essential for parasite growth and apicoplast biology, conditional disruption of PIKfyve induces enlarged apicoplasts, as observed upon the loss of PI(3)P. A similar defect of apicoplast homeostasis was also observed by knocking-down the PIKfyve regulatory protein ArPIKfyve, suggesting that in T. gondii, PI(3)P-related function for the apicoplast might mainly be to serve as a precursor for the synthesis of PI(3,5)P₂ . Accordingly, PI3K is conserved in all apicomplexan parasites whereas PIKfyve and ArPIKfyve are absent in Cryptosporidium species which lack an apicoplast, supporting a direct role of PI(3,5)P₂ in apicoplast homeostasis. This study enriches the already diverse functions attributed to PI(3,5)P₂ in eukaryotic cells and highlights these parasite lipid kinases as potential drug targets.
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KEYWORDS:

Apicomplexa; Apicoplast biogenesis; Delayed death phenotype; Lipid modifications; Phosphoinositides; Tet-inducible system; Toxoplasma gondii; Traffic

PMID:

25329540

[PubMed - as supplied by publisher]