Nuclear transport inEntamoeba histolytica: knowledge gap and therapeutic potential

Abstract

Entamoeba histolytica is the protozoan parasite that causes human amoebiasis. It is one of the leading parasitic disease burdens in tropical regions and developing countries, with spread to developed countries through migrants from and travellers to endemic regions.Understanding E. histolytica's invasion mechanisms requires an understanding of how it interacts with external cell components and how it engulfs and kills cells (phagocytosis). Recent research suggests that optimal phagocytosis requires signalling events from the cell surface to the nucleus via the cytoplasm, and the induction of several factors that are transported to the plasma membrane. Current research in other protozoans suggests the presence of proteins with nuclear localization signals, nuclear export signals and Ran proteins; however, there is limited literature on their functionality and their functional similarity to higher eukaryotes.Based on learnings from the development of antivirals, nuclear transport elements in E. histolytica may present viable, specific, therapeutic targets.In this review, we aim to summarize our limited knowledge of the eukaryotic nuclear transport mechanisms that are conserved and may function in E. histolytica.

Multiple types of nuclear localization signals in Entamoeba histolytica

“…Furthermore, the presence of nuclear transport factors in E. histolytica ( Fig. 6 ) reinforces the hypothesis that nuclear transport mediated by the canonical nuclear protein import pathway is present from an early stage of eukaryotic evolution, as observed in phylogenetic analyses of Importin α conservation and Importin β in yeast and mammalian species members of the supergroup Opisthokonta [ 28 , 49 , 55 ]. The fact that we identified the EhCAS Exportin (CCR1), Ran, RanBP1, RandGAP, RanGEF, and NTF2 annotated in the E. histolytica genome indicates that the nuclear protein export process is present being supported by the fact that the protein EhNCABP166 contains a functional NES rich in Leucines and the Ehp53 protein that has anNES of the same type and EhRhoGAPnc as well [ 33 , 35 , 37 ] however they need to be tested experimentally.…”

Functional Characterization of Entamoeba histolytica Argonaute Proteins Reveals a Repetitive DR-Rich Motif Region That Controls Nuclear Localization

“…In Entamoeba , molecular determinants for the protein trafficking into the nucleus are not well studied (44). The typical classical nuclear localization sequences (NLS of the simian virus 40 [SV40] large T antigen) do not appear to work for amebic parasites (reference 44 and data not shown). The previously described NLS from an E.…”

Entamoeba histolytica protein CaBP3 uses a calcium dependent nuclear localisation pathway in mammalian cells

“…Whole genome analysis of E. histolytica has shown the presence of putative protein components of the nuclear trafficking machinery. Indeed, our bioinformatics investigations predict the presence of all the core components of Ran dependent nuclear transport (Gwairgi & Ghildyal, 2018).…”