ArPIKfyve

ArPIKfyve is a regulatory component of the PIKfyve lipid kinase complex in Toxoplasma gondii required for apicoplast homeostasis (PMID:25329540). Conditional depletion of ArPIKfyve causes enlarged apicoplasts, phenocopying loss of PIKfyve itself and PI(3)P depletion, indicating that ArPIKfyve acts as part of a regulatory complex that supports PIKfyve-mediated synthesis of PI(3,5)P2 from PI(3)P (PMID:25329540). Beyond this genetic phenotype, no further biochemical or structural detail of ArPIKfyve has been characterized in the available corpus.

1. 2014 Medium

   It was unknown whether the PIKfyve regulatory subunit contributes to organelle maintenance in Toxoplasma; conditional knockdown showed ArPIKfyve loss enlarges apicoplasts, establishing it as a required regulator of apicoplast homeostasis within the PIKfyve lipid kinase complex.

   Evidence Conditional inducible knockdown with apicoplast morphology readout in T. gondii

   PMID:25329540

   Open questions at the time

   • Direct biochemical demonstration that ArPIKfyve stimulates PIKfyve-mediated PI(3,5)P2 synthesis is not shown
   • The physical interaction between ArPIKfyve and PIKfyve is inferred from phenocopy, not demonstrated
   • The mechanism linking PI(3,5)P2 levels to apicoplast size and inheritance is not defined

• How ArPIKfyve activates PIKfyve at the molecular level, and how the resulting PI(3,5)P2 pool controls apicoplast size and organelle inheritance, remains unresolved.
• No direct binding or reconstitution data for the ArPIKfyve–PIKfyve complex
• No measurement of PI(3,5)P2 levels upon ArPIKfyve depletion
• Subcellular localization of ArPIKfyve not established