Identification and characterization of a novel StAR-related lipid transfer protein in Entamoeba histolytica that shuttles phosphoinositides between the nucleus and the cytoplasm: role in growth, stress defense, membrane traffick, and pathogenesis.

Phospholipids, their biosynthesis, and functional implications in the nucleus have been recently unraveled from eukaryotes. However, how the phospholipid precursors are trafficked between the nucleus and the cytoplasm and how nuclear lipids are synthesized sis and degradedation is regulated for homeostasis in the eukaryotic cell still largely unknown. In the present study, we have identified for the first time a lipid transfer protein (LTP) from a protozoan parasite E. histolytica (EhLTP15) that is involved in nuclear-cytoplasmic lipid transport and regulation of nuclear lipid metabolism and homeostasis. EhLTP15 translocated from the nucleus to the cytoplasm under nutrient deprived conditions, which mimics encystation conditions, thus can potentially functions as intracellular communicator during stage conversion. EhLTP15 was also involved in exocytosis of pinocytosed fluid phase maker and secretion of lysosomal enzymes, cysteine proteases, which are implicated for virulence and tissue invasion of this enteric pathogen. EhLTP15 was also involved in the defense against oxidative stress. Furthermore, EhLTP15 was necessary to maintain the levels of nuclear phosphoinositides. This study has provided a link between non-vesicular lipid transport and nuclear lipid metabolism for the first time in any unicellular eukaryotes. To investigate the effects of gene silencing we established cells lines in which target gene has been gene silenced by epigenetic silencing. We then performed gene expression analysis using the data obtained from the RNA-seq of pSAP (mock transfected), LTP15 gene silenced strains (n=3)