A Proteomic and Cellular Analysis of Uropods in the Pathogen Entamoeba histolytica

Markiewicz, Jacques Marquay; Syan, Sylvie; Hon, Chung-Chau; Weber, Christian; Faust, Daniela M.; Guillén, Nancy

doi:10.1371/journal.pntd.0001002

Cited by 33 publications

(43 citation statements)

References 67 publications

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“…3, C and D). However, this low micromolar affinity EhRho1/EhFormin1 interaction is likely relevant in a cellular context, given the observed stringent nucleotide state selectivity and previous evidence for colocalization of both proteins in the E. histolytica uropod (48). We conclude that EhRho1 engages similar effectors to mammalian Rho family GTPases.…”

Section: Figure 1 Sequence Similarity Among Rho and Ras Family Gtpasmentioning

confidence: 52%

“…EhFormin1 localizes with actin filaments in E. histolytica trophozoites upon exposure to serum factors (19) and is co-enriched with EhRho1 in the uropod, suggesting roles for the EhRho1⅐EhFormin1 complex in amoebic motility and/or surface receptor capping (48). EhFormin1 also co-localizes with microtubules during mitosis, and its overexpression leads to delays in cell cycle progression (20).…”

Section: Discussionmentioning

confidence: 99%

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Unique Structural and Nucleotide Exchange Features of the Rho1 GTPase of Entamoeba histolytica

Bosch

Wittchen

Connie

et al. 2011

Journal of Biological Chemistry

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Background: Rho family GTPases regulate Entamoeba histolytica pathogenesis. Results: Despite Ras-like structural features and fast intrinsic nucleotide exchange, EhRho1 engages classical Rho effectors and regulates actin. Conclusion: EhRho1 is a true Rho family GTPase with a unique mode of nucleotide interaction. Significance: Possibly representing an early Rho subfamily divergence from the Ras superfamily, EhRho1 likely regulates actin polymerization in E. histolytica.

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Section: Figure 1 Sequence Similarity Among Rho and Ras Family Gtpasmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Unique Structural and Nucleotide Exchange Features of the Rho1 GTPase of Entamoeba histolytica

Bosch

Wittchen

Connie

et al. 2011

Journal of Biological Chemistry

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“…PI(4,5)P 2 can function as a second messenger and bind various actin-binding proteins. A proteomic analysis of E. histolytica uroids identified the presence of actin-binding proteins that have been reported to interact with PI(4,5)P 2 in other eukaryotic cells, including the spectrin-family proteins (e.g., filamin 2, an actininlike protein) and a novel protein, filopodin (53). In other systems, PI(4,5)P 2 has been shown to regulate actin cytoskeleton by binding and modulating filamin (54) and ␣-actinin (55).…”

Section: Discussionmentioning

confidence: 99%

Localization of Phosphatidylinositol 4,5-Bisphosphate to Lipid Rafts and Uroids in the Human Protozoan Parasite Entamoeba histolytica

2013

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bEntamoeba histolytica is an intestinal protozoan parasite and is the causative agent of amoebiasis. During invasive infection, highly motile amoebae destroy the colonic epithelium, enter the blood circulation, and disseminate to other organs such as liver, causing liver abscess. Motility is a key factor in E. histolytica pathogenesis, and this process relies on a dynamic actomyosin cytoskeleton. In other systems, phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] is known to regulate a wide variety of cellular functions, including signal transduction, actin remodeling, and cell motility. Little is known about the role of PI(4,5)P 2 in E. histolytica pathogenicity. In this study, we demonstrate that PI(4,5)P 2 is localized to cholesterol-rich microdomains, lipid rafts, and the actin-rich fractions of the E. histolytica membrane. Microscopy revealed that the trailing edge of polarized trophozoites, uroids, are highly enriched in lipid rafts and their constituent lipid, PI(4,5)P 2 . Polarization and enrichment of uroids and rafts with PI(4,5)P 2 were enhanced upon treatment of E. histolytica cells with cholesterol. Exposure to cholesterol also increased intracellular calcium, which is a downstream effector of PI(4,5)P 2 , with a concomitant increase in motility. Together, our data suggest that in E. histolytica, PI(4,5)P 2 may signal from lipid rafts and cholesterol may play a role in triggering PI(4,5)P 2 -mediated signaling to enhance the motility of this pathogen.T he intestinal parasite Entamoeba histolytica is known to cause amoebic dysentery and liver abscess. E. histolytica enters the human host via contaminated food or water as an environmentally stable cyst. Excystation leads to the release of trophozoites in the small intestine, which colonize the bowel lumen. From here, the parasite can enter two non-mutually exclusive routes of infection, noninvasive or invasive disease (reviewed in reference 1). In the noninvasive mode, the trophozoite encysts and exits the host, whereas in the invasive mode, the parasite adheres to and destroys the colonic epithelium and enters the circulatory system. This results in extraintestinal infection, of which amoebic liver abscess (ALA) is the most common manifestation. Motility is a key virulence function that enables this parasite to cause extraintestinal infection (2).Motile amoebae display a polarized morphology with a pseudopod at the leading edge and a uroid (also referred to as a uropod in other eukaryotic cells) at the trailing edge. A key feature of a polarized cell is the differential distribution of proteins and lipids, including cell surface receptors, signaling molecules, and cytoskeletal elements. For example, the pseudopod of E. histolytica is enriched in F actin, myosin IB (3, 4), and signaling molecules like phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P 3 ] (5), while the uroid is enriched in myosin II and signaling molecules, including an important heterotrimeric adhesin, the galactose/N-acetylgalactosamine (Gal/GalNAc) lectin (6), F actin, and var...

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“…A proteomic analysis of uropod components in fact showed the abundance of factors such as the Gal/GalNAc lectin and several CPs [33]. Using amoebic strains silenced for CP-A5 gene expression and parasites blocked for Gal/GalNAc lectin activity, we have identified these functions as important factors involved in parasite adhesion, LSEC retraction and death.…”

Section: European Journal Of Microbiology and Immunology 1 (2011)mentioning

confidence: 97%

New insights into host-pathogen interactions duringEntamoeba histolyticaliver infection

Faust¹,

Markiewicz²,

Santi-Rocca³

et al. 2011

European Journal of Microbiology and Immunology

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Amoebiasis is the third worldwide disease due to a parasite. The causative agent of this disease, the unicellular eukaryote Entamoeba histolytica, causes dysentery and liver abscesses associated with inflammation and human cell death. During liver invasion, before entering the parenchyma, E. histolytica trophozoites are in contact with liver sinusoidal endothelial cells (LSEC). We present data characterizing human LSEC responses to interaction with E. histolytica and identifying amoebic factors involved in the process of cell death in this cell culture model potentially relevant for early steps of hepatic amoebiasis. E. histolytica interferes with host cell adhesion signalling and leads to diminished adhesion and target cell death. Contact with parasites induces disruption of actin stress fibers and focal adhesion complexes. We conclude that interference with LSEC signalling may result from amoeba-triggered changes in the mechanical forces in the vicinity of cells in contact with parasites, sensed and transmitted by focal adhesion complexes. The study highlights for the first time the potential role in the onset of hepatic amoebiasis of the loss of liver endothelium integrity by disturbance of focal adhesion function and adhesion signalling. Among the amoebic factors required for changed LSEC adherence properties we identified the Gal/GalNAC lectin, cysteine proteases and KERP1.

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A Proteomic and Cellular Analysis of Uropods in the Pathogen Entamoeba histolytica

Cited by 33 publications

References 67 publications

Unique Structural and Nucleotide Exchange Features of the Rho1 GTPase of Entamoeba histolytica

Unique Structural and Nucleotide Exchange Features of the Rho1 GTPase of Entamoeba histolytica

Localization of Phosphatidylinositol 4,5-Bisphosphate to Lipid Rafts and Uroids in the Human Protozoan Parasite Entamoeba histolytica

New insights into host-pathogen interactions duringEntamoeba histolyticaliver infection

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