Intracellular traffic of the lysine and glutamic acid rich protein KERP1 reveals features of endomembrane organization inEntamoeba histolytica

Abstract

The development of amoebiasis is influenced by the expression of the lysine and glutamic acid rich protein 1 (KERP1), a virulence factor involved in Entamoeba histolytica adherence to human cells. Up to date, it is unknown how the protein transits the parasite cytoplasm towards the plasma membrane, specially because this organism lacks a well-defined endoplasmic reticulum (ER) and Golgi apparatus. In this work we demonstrate that KERP1 is present at the cell surface and in intracellular vesicles which traffic in a pathway that is independent of the ER-Golgi anterograde transport. The intracellular displacement of vesicles enriched in KERP1 relies on the actin-rich cytoskeleton activities. KERP1 is also present in externalized vesicles deposited on the surface of human cells. We further report the interactome of KERP1 with its association to endomembrane components and lipids. The model for KERP1 traffic here proposed hints for the first time elements of the endocytic and exocytic paths of E. histolytica.

EhRabB mobilises the EhCPADH complex through the actin cytoskeleton during phagocytosis of Entamoeba histolytica

“…Phagocytosis is one of the main functions expressed during destruction of the epithelia by the trophozoites. Membrane proteins participating in these events have been already identified, among them the Gal/GalNac lectin (Petri, Haque, & Mann, ), the EhCPADH complex (Garcia‐Rivera et al, ), the KERP1 protein (Perdomo et al, ), and others (Garcia‐Rivera et al, ; Laughlin & Temesvari, ; Pillai & Kain, ). EhCPADH is formed by the proteins EhCP112 (446 amino acids) and EhADH (687 amino acids), which belongs to the ALIX family.…”

EhNPC1 and EhNPC2 Proteins Participate in Trafficking of Exogenous Cholesterol in Entamoeba histolytica Trophozoites: Relevance for Phagocytosis

“…histolytica ALIX family protein) [25] inside phagolysosomes and multivesicular bodies (MVB) [26]. Though, we do not discard the participation of other Alix proteins involved in endomembrane trafficking [27, 28]. Thus, it is plausible to assume that the “hand-off” model, “NPC2-NPC1-cholesterol-NPC2-NPC1” proposed for mammalian cells, could also be functioning in trophozoites to first carry exogenous cholesterol inside the cell and then, to transport it to distinct organelles.…”

Entamoeba histolytica under Oxidative Stress: What Countermeasure Mechanisms Are in Place?

“…Notably, there is an active engagement of the E. histolytica cytoskeleton to provide backup for the amoebic survival functions (i.e., motility, erythrophagocytosis) and, more likely, although not yet explored, a relevant role in the endomembrane dynamics. Experiments have shown that there is an active engagement from the cytoskeleton and secretion pathway to deliver virulence factors to the plasma membrane, even under chemical stress conditions [ 69 , 87 ]. This process is contrary to what is detailed in mammalian cells, where the ER limits the folding and secretion when under stress to prevent ER overload.…”

“…Motility is an essential function for the survival of E. histolytica [ 67 , 68 ] not only for displacement and phagocytosis of host cells, but also for the intracellular trafficking of virulence factors [ 69 ]. Another project correlating the transcriptomic data of NO-exposed parasites to the proteomic data of NO-adapted trophozoites [ 70 ] showed an up-regulation in the gene expression of cytoskeleton proteins that were previously identified by proteomics.…”