Cholesterol starvation induces differentiation of the intestinal parasite Giardia lamblia.

Luján, Hugo D.; Mowatt, Michael R.; Byrd, Linda G.; Nash, Theodore E.

doi:10.1073/pnas.93.15.7628

Cited by 127 publications

(115 citation statements)

References 47 publications

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“…Surprisingly, these cultures displayed a 2.2-fold increase in cyst number. Because Giardia encystation can be triggered by lipoprotein deprivation (38), the function of actin in LDL uptake is consistent with reduced perception of LDL and the increased encystation efficiency of actin knockdown cultures. To assay the integrity of actin knockdown cysts, we treated encysted cultures with water to lyse any nonencysted cells and then measured cyst wall integrity/viability by staining with trypan blue.…”

Section: Resultsmentioning

confidence: 87%

An actin cytoskeleton with evolutionarily conserved functions in the absence of canonical actin-binding proteins

Paredez

Assaf

Sept

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

166

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Giardia intestinalis, a human intestinal parasite and member of what is perhaps the earliest-diverging eukaryotic lineage, contains the most divergent eukaryotic actin identified to date and is the first eukaryote known to lack all canonical actin-binding proteins (ABPs). We sought to investigate the properties and functions of the actin cytoskeleton in Giardia to determine whether Giardia actin (giActin) has reduced or conserved roles in core cellular processes. In vitro polymerization of giActin produced filaments, indicating that this divergent actin is a true filament-forming actin. We generated an anti-giActin antibody to localize giActin throughout the cell cycle. GiActin localized to the cortex, nuclei, internal axonemes, and formed C-shaped filaments along the anterior of the cell and a flagella-bundling helix. These structures were regulated with the cell cycle and in encysting cells giActin was recruited to the Golgi-like cyst wall processing vesicles. Knockdown of giActin demonstrated that giActin functions in cell morphogenesis, membrane trafficking, and cytokinesis. Additionally, Giardia contains a single G protein, giRac, which affects the Giardia actin cytoskeleton independently of known target ABPs. These results imply that there exist ancestral and perhaps conserved roles for actin in core cellular processes that are independent of canonical ABPs. Of medical significance, the divergent giActin cytoskeleton is essential and commonly used actin-disrupting drugs do not depolymerize giActin structures. Therefore, the giActin cytoskeleton is a promising drug target for treating giardiasis, as we predict drugs that interfere with the Giardia actin cytoskeleton will not affect the mammalian host. cytoskeleton evolution | actin protofilaments | MreB | endocytosis | Rac

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Section: Resultsmentioning

confidence: 87%

An actin cytoskeleton with evolutionarily conserved functions in the absence of canonical actin-binding proteins

Paredez

Assaf

Sept

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

166

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“…This process involves cellular and molecular events. Luján et al (1996) reported that cholesterol starvation induces encystation.…”

Section: Introductionmentioning

confidence: 99%

“…Three encystation-specific cyst wall proteins (CWP1, 2 and 3) are expressed and concentrated in encystation-specific-vesicles (ESVs) that circulate within the parasite before being transported to the cyst wall (Luján et al, 1996;Reiner et al, 1990;Lauwaet et al, 2007;Faso and Hehl, 2011;Benchimol and De Souza, 2011). Synthesis of ESVs starts 4-6 h after encystation is induced and is completed with the cyst formation by approximately 24 h (Reiner et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Microvesicles released from Giardia intestinalis disturb host-pathogen response in vitro

Evans-Osses

Mojoli

Monguió‐Tortajada

et al. 2017

European Journal of Cell Biology

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a b s t r a c tGiardia intestinalis (G.I), is an anaerobic protozoan and the aetiological agent of giardiasis, a diarrhoea present worldwide and associated with poverty. G.I has a simple life cycle alternating between cyst and trophozoite. Cysts are transmitted orally to the stomach and transform to trophozoites in the intestine by a multifactorial process. Recently, microvesicles (MVs) have been found to be released from a wide range of eukaryotic cells. We have observed a release of MVs during the life cycle of G.I., identifying MVs from active trophozoites and from trophozoites differentiating to the cyst form. The aim of the current work was to investigate the role of MVs from G.I in the pathogenesis of giardiasis. MVs from log phase were able to increase the attachment of G. intestinalis trophozoites to Caco-2 cells. Moreover, MVs from G. intestinalis could be captured by human immature dendritic cells, resulting in increased activation and allostimulation of human dendritic cells. Lipid rafts participate in the MV biogenesis and in the attachment to Caco-2 cells. Nevertheless, proteomic analysis from two types of MVs has shown slight differences at the protein levels. An understanding of biogenesis and content of MVs derived from trophozoites might have important implications in the pathogenesis of the disease.

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“…This process ends when the cysts enter the small intestine, where the trophozoites emerge and adhere to the duodenum and jejunum surfaces and multiply by binary fission. Some trophozoites travel along the intestinal tract and are induced to encyst, probably triggered by the high pH, the presence of bile salts, and a low cholesterol concentration (5). These cysts are excreted in the stools and thereby become available for ingestion by another host to complete the cycle (1,6,7).…”

Section: Synthesis Of Two Metabolic Enzymes During G Intestinalis Exmentioning

confidence: 99%

Síntesis de las enzimas de piruvato, oxidorreductasa de ferredoxina y deshidrogenasa E de alcohol durante el desenquistamiento (excystacion) de Giardia intestinalis

Niño

Wasserman

2010

biomedica

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Introduction. Giardia intestinalis is a unicellular parasite of worldwide distribution. It causes an intestinal illness known as giardiasis, and it is probably the earliest diverging eukaryotic microorganism. Previously, changes have been reported in the expression of mRNAs at several stages of the life cycle; however specific enzymatic activity changes have not been explored. Objective. The expression of pyruvate ferredoxin oxidoreductase (PFOR) and alcohol dehydrogenase E (ADHE) enzymes was measured in cyst and trophozoite stages, and during the excystation process. Materials and methods. Recombinant proteins were generated for PFOR and ADHE to be used as antigens in the production of polyclonal antibodies for the detection of native proteins by Western Blot. The enzymatic activity of ADHE and glutamate dehydrogenase (GDH) was evaluated by spectrophotometric assays. Results. PFOR (139 kDa) and ADHE (97 kDa) proteins were detected in trophozoites, but not in cysts. During excystation, ADHE protein was detected after the first phase of induction, but the PFOR protein appeared only after the second phase. This indicated that both proteins were synthesized during excystation, although at different times. ADHE enzymatic activity was present only in trophozoites and not in cysts whereas GDH activity was detected in both stages. Conclusion. These results conclusively showed that PFOR and ADHE enzymes were translated during the excystation process and is strong evidence that active protein synthesis was occurring during excystation.

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Cholesterol starvation induces differentiation of the intestinal parasite Giardia lamblia.

Cited by 127 publications

References 47 publications

An actin cytoskeleton with evolutionarily conserved functions in the absence of canonical actin-binding proteins

An actin cytoskeleton with evolutionarily conserved functions in the absence of canonical actin-binding proteins

Microvesicles released from Giardia intestinalis disturb host-pathogen response in vitro

Síntesis de las enzimas de piruvato, oxidorreductasa de ferredoxina y deshidrogenasa E de alcohol durante el desenquistamiento (excystacion) de Giardia intestinalis

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