Characterization of a putative Plasmodium falciparum SAC1 phosphoinositide-phosphatase homologue potentially required for survival during the asexual erythrocytic stages

Sci Rep. 2017 Oct 5;7(1):12710. doi: 10.1038/s41598-017-12762-0.

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.

MeSH terms

  • Animals
  • Antimalarials / pharmacology
  • Cytokinesis
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / parasitology
  • Erythrocytes / enzymology*
  • Erythrocytes / parasitology
  • Golgi Apparatus / genetics
  • Golgi Apparatus / parasitology
  • Humans
  • Life Cycle Stages / genetics
  • Malaria, Falciparum / blood
  • Malaria, Falciparum / genetics*
  • Malaria, Falciparum / parasitology
  • Phosphoinositide Phosphatases / antagonists & inhibitors
  • Phosphoinositide Phosphatases / genetics*
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / pathogenicity
  • Protozoan Proteins / antagonists & inhibitors
  • Protozoan Proteins / genetics*

Substances

  • Antimalarials
  • Protozoan Proteins
  • Phosphoinositide Phosphatases