Phosphatidylinositol Kinases and Phosphatases in Entamoeba histolytica

Abstract

Phosphatidylinositol (PtdIns) metabolism is indispensable in eukaryotes. Phosphoinositides (PIs) are phosphorylated derivatives of PtdIns and consist of seven species generated by reversible phosphorylation of the inositol moieties at the positions 3, 4, and 5. Each of the seven PIs has a unique subcellular and membrane domain distribution. In the enteric protozoan parasite Entamoeba histolytica , it has been previously shown that the PIs phosphatidylinositol 3-phosphate (PtdIns3P), PtdIns(4,5)P 2 , and PtdIns(3,4,5)P 3 are localized to phagosomes/phagocytic cups, plasma membrane, and phagocytic cups, respectively. The localization of these PIs in E. histolytica is similar to that in mammalian cells, suggesting that PIs have orthologous functions in E. histolytica . In contrast, the conservation of the enzymes that metabolize PIs in this organism has not been well-documented. In this review, we summarized the full repertoire of the PI kinases and PI phosphatases found in E. histolytica via a genome-wide survey of the current genomic information. E. histolytica appears to have 10 PI kinases and 23 PI phosphatases. It has a panel of evolutionarily conserved enzymes that generate all the seven PI species. However, class II PI 3-kinases, type II PI 4-kinases, type III PI 5-phosphatases, and PI 4P-specific phosphatases are not present. Additionally, regulatory subunits of class I PI 3-kinases and type III PI 4-kinases have not been identified. Instead, homologs of class I PI 3-kinases and PTEN, a PI 3-phosphatase, exist as multiple isoforms, which likely reflects that elaborate signaling cascades mediated by PtdIns(3,4,5)P 3 are present in this organism. There are several enzymes that have the nuclear localization signal: one phosphatidylinositol phosphate (PIP) kinase, two PI 3-phosphatases, and one PI 5-phosphatase; this suggests that PI metabolism also has conserved roles related to nuclear functions in E. histolytica , as it does in model organisms.

Dynamism of PI4-Phosphate during Interactions with Human Erythrocytes in Entamoeba histolytica

“…However, the two former metabolites are unlikely to be produced from PI4P because neither PI4-phosphatase nor Type II PI3-kinase is present in the E. histolytica genome. On the contrary, PI(4,5)P 2 can be synthesized from PI4P, as E. histolytica has Type II PI5-kinase (EHI_153770), which contains a potential nuclear localization signal (NLS) [ 15 ]. PI(4,5)P 2 is further metabolized to DAG and inositol 3-phosphate (IP 3 ) by phospholipase C (PLC).…”

Revisiting Drug Development Against the Neglected Tropical Disease, Amebiasis

“…Although PI phosphorylation and dephosphorylation have been recently started to be explored, it is tentative to assume that detailed analysis of kinases and phosphatases might lead to a drug target of choice. The kinases involved in PI machinery of Entamoeba are distinct from their mammalian counterparts, which is helpful in making such an assumption ( Nakada-Tsukui et al., 2019 ).…”

Anaerobic peroxisomes in Entamoeba histolytica metabolize myo-inositol

“…The matrix of E. histolytica peroxisomes contains myo-IDH, which catalyzes reversible NAD + -dependent conversion of myo-inositol to keto-2-inositol.Myo-inositol is synthesized from glucose-6-phosphate by the activity of inositol 3-phosphate synthase and inositol-3-phosphatase, which are both present in E. histolytica. Myo-inositol is utilized for the synthesis of phosphatidylinositol and a spectrum of phosphoinositide derivatives that are produced by a set of phosphatidylinositol kinases and phosphatases [72,73]. These compounds have multiple roles as components of membrane lipids, they are used in cell signaling pathways, energy homeostasis, and as cytoprotective solutes [74,75].…”