Entamoeba histolytica: Lipid rafts are involved in adhesion of trophozoites to host extracellular matrix components

Mittal, Kriti; Welter, Brenda H.; Temesvari, Lesly A.

doi:10.1016/j.exppara.2008.06.003

Cited by 38 publications

(33 citation statements)

References 51 publications

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“…There are intriguing correlations between E. histolytica virulence and cholesterol. For example, cholesterol has been shown to enhance virulence functions in E. histolytica, including adhesion (27,28), expression of ConA binding sites on the cell surface (63), and hemolytic and erythrophagocytic activity (64). Several studies have demonstrated that it is possible to revive the virulence of avirulent E. histolytica strains by supplying medium with cholesterol (65,66) or by repeated passage through liver, which is a major site of cholesterol synthesis (67).…”

Section: Discussionmentioning

confidence: 99%

“…Dialkyindocarbocyanine (DiIC 16 ; Invitrogen) staining of lipid rafts was carried out as described previously (27).…”

Section: Methodsmentioning

confidence: 99%

“…Since our biochemical analysis demonstrated that lipid rafts were enriched in PI(4,5)P 2 and since microscopy revealed that PI(4,5)P 2 localized to uroids, we wanted to determine if, like in mammalian cells (40), the uroids of E. histolytica were enriched in lipid rafts. Therefore, we employed a lipid raft stain, DiIC 16 , on fixed E. histolytica trophozoites as previously described (27). Cells with no apparent pseudopod formation (nonpolarized) displayed a uniform plasma membrane raft staining ( Fig.…”

Section: Figmentioning

confidence: 99%

“…Rafts are specialized membrane microdomains that are cho-lesterol and sphingolipid rich and are known to organize signaling molecules that participate in a variety of cellular functions, including cell polarization (21,22), endocytosis (reviewed in reference 23), secretion (reviewed in reference 24), and adhesion (25). Previously, E. histolytica was shown to possess lipid rafts that regulate parasite-host interaction (26,27). Disruption of rafts with cholesterol-binding agents like methyl-␤-cyclodextrin (M␤CD) inhibits adhesion of E. histolytica to host cells (26) and host extracellular matrix components (27).…”

mentioning

confidence: 99%

“…Previously, E. histolytica was shown to possess lipid rafts that regulate parasite-host interaction (26,27). Disruption of rafts with cholesterol-binding agents like methyl-␤-cyclodextrin (M␤CD) inhibits adhesion of E. histolytica to host cells (26) and host extracellular matrix components (27). On the other hand, cholesterol loading of amoebic membranes results in enhanced adhesion to host cell monolayers, as well as cocompartmentalization of the three subunits of the Gal/GalNAc lectin in lipid rafts (28).…”

mentioning

confidence: 99%

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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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