Background: Phosphoinositides (PIs) and their derivatives are essential cellular components
that form the building blocks for cell membranes and regulate numerous cell functions. Specifically,
the ability to generate myo-inositol 1,4,5-trisphosphate (InsP3) via phospholipase C (PLC) dependent
hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to InsP3 and diacylglycerol
(DAG) initiates intracellular calcium signaling events representing a fundamental signaling mechanism
dependent on PIs. InsP3 produced by PI turnover as a second messenger causes intracellular calcium
release, especially from endoplasmic reticulum, by binding to the InsP3 receptor (InsP3R). Various
PIs and the enzymes, such as phosphatidylinositol synthase and phosphatidylinositol 4-kinase,
necessary for their turnover have been characterized in Apicomplexa, a large phylum of mostly commensal
organisms that also includes several clinically relevant parasites. However, InsP3Rs have not
been identified in genomes of apicomplexans, despite evidence that these parasites produce InsP3 that
mediates intracellular Ca2+ signaling.
Conclusion: Evidence to supporting IP3-dependent signaling cascades in apicomplexans suggests that
they may harbor a primitive or non-canonical InsP3R. Understanding these pathways may be informative
about early branching eukaryotes, where such signaling pathways also diverge from animal systems,
thus identifying potential novel and essential targets for therapeutic intervention.