Abstract
Despite marked reductions in morbidity and mortality in the last ten years, malaria still takes a tremendous toll on human populations throughout tropical and sub-tropical regions of the world. The absence of an effective vaccine and resistance to most antimalarial drugs available demonstrate the urgent need for new intervention strategies. Phosphoinositides are a class of lipids with critical roles in numerous processes and their specific subcellular distribution, generated through the action of kinases and phosphatases, define organelle identity in a wide range of eukaryotic cells. Recent studies have highlighted important functions of phosphoinositide kinases in several parts of the Plasmodium lifecycle such as hemoglobin endocytosis and cytokinesis during the erythrocytic stage however, nothing is known with regards to the parasite’s putative phosphoinositide phosphatases. We present the identification and initial characterization of a putative homologue of the SAC1 phosphoinositide phosphatase family. Our results show that the protein is expressed throughout the asexual blood stages and that it localises to the endoplasmic reticulum and potentially to the Golgi apparatus. Furthermore, conditional knockdown and knockout studies suggest that a minimal amount of the protein are likely required for survival during the erythrocytic cycle.
Highlights
Malaria is one of the most important infectious diseases worldwide with nearly half of the world’s population being at risk of contracting it[1]
Our results show that PfSAC1 is expressed throughout the asexual blood stages, that it localises to the endoplasmic reticulum and is enriched at or close to the Golgi apparatus
To identify putative P. falciparum homologues of the S. cerevisiae SAC1 phosphoinositide-phosphatase, a BLAST analysis was performed in the PlasmoDB database using the full-length protein sequence
Summary
Malaria is one of the most important infectious diseases worldwide with nearly half of the world’s population being at risk of contracting it[1]. Despite being only minor components of cellular membranes, phosphoinositides (PIPs) play critical roles in numerous processes such as signal transduction, cell motility, cytoskeletal reorganisation, DNA synthesis, cell cycle regulation, adhesion, membrane transport, permeability and trafficking[6,7] These lipids are found in seven isoforms depending on which positions on the inositol ring are phosphorylated through the action of kinases and phosphatases (reviewed in[8]). In contrast to PIP kinases, nothing is known with regards to the parasite’s four putative PIP phosphatases identified through bioinformatics analysis[15] Among these putative PIP phosphatases is a homolog of SAC1 (PF3D7_1354200), an enzyme cycling between the endoplasmic reticulum and the Golgi apparatus in yeast and mammalian cells with activity against PIP monophosphates[16,17]. Despite the fact that strongly decreasing PfSAC1 expression has no effect on parasite growth, our inability to inactivate the PfSAC1 gene by regular knock out suggests that minimal amounts of the enzyme are essential for in vitro survival
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
