ALBA proteins are stage regulated during trypanosome development in the tsetse fly and participate in differentiation

Subota, Ines; Rotureau, Brice; Blisnick, Thierry; Ngwabyt, Sandra; Durand-Dubief, Mickaël; Engstler, Markus; Bastin, Philippe

doi:10.1091/mbc.e11-06-0511

Cited by 94 publications

(109 citation statements)

References 67 publications

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“…The posterior and anterior midgut, the proventriculus and foregut were checked for the presence of parasites under the microscope. Similar to our previous studies 2012;Subota et al, 2011), parasites were found in 45% of the posterior midguts, 11% of the anterior midguts, and 4% of the foreguts of flies fed with WT trypanosomes (Fig. 3A).…”

Section: Dnai1 Mutant Parasites Are Unable To Reach the Foregut Of Thsupporting

confidence: 90%

Forward motility is essential for trypanosome infection in the tsetse fly

et al. 2013

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SummaryAfrican trypanosomes are flagellated protozoan parasites transmitted by the bite of tsetse flies and responsible for sleeping sickness in humans. Their complex development in the tsetse digestive tract requires several differentiation and migration steps that are thought to rely on trypanosome motility. We used a functional approach in vivo to demonstrate that motility impairment prevents trypanosomes from developing in their vector. Deletion of the outer dynein arm component DNAI1 results in strong motility defects but cells remain viable in culture. However, although these mutant trypanosomes could infect the tsetse fly midgut, they were neither able to reach the foregut nor able to differentiate into the next stage, thus failing to complete their parasite cycle. This is the first in vivo demonstration that trypanosome motility is essential for the accomplishment of the parasite cycle.

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Section: Dnai1 Mutant Parasites Are Unable To Reach the Foregut Of Thsupporting

confidence: 90%

Forward motility is essential for trypanosome infection in the tsetse fly

et al. 2013

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“…2), we speculate that either TbSAS-4 is not expressed or its level is significantly reduced in the epimastigote cells differentiated from trypomastigote cells in the tsetse fly vector. Although the expression levels of TbSAS-4 in the two developmental forms are not known, TbSAS-4 mRNA is among the most highly down-regulated transcripts during the differentiation to epimastigote cells by ablation of ALBA3/4 (45), RNA-binding proteins that are also involved in cell morphology transitions (27). Similarly, ClpGM6 mRNA was also down-regulated by depletion of ALBA3/4 (15,45).…”

Section: Discussionmentioning

confidence: 99%

“…How life cycle transitions in T. brucei are regulated is largely unknown, but recent work has begun to uncover the regulators involved in this process. ALBA3 and ALBA4, two closed related RNA-binding proteins, are the first factors found to be involved in life cycle transitions in T. brucei (27). Another RNA-binding protein, RBP6, is also required for driving the transition from trypomastigotes to epimastigotes (28).…”

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confidence: 99%

SAS-4 Protein in Trypanosoma brucei Controls Life Cycle Transitions by Modulating the Length of the Flagellum Attachment Zone Filament

Zhou

2015

Journal of Biological Chemistry

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The centrosome in animals constitutes the cell's microtubule-organizing center that nucleates spindle assembly, and is characterized by a symmetrical array of nine microtubule triplets emanating from a cartwheel structure in the very proximal region of the centriole. Biogenesis of centrioles requires many regulatory proteins, including SAS-6, SAS-4/CPAP, and BLD10/CEP135, which are thought to constitute the core ancestral module involved in centriole assembly (1). The three proteins have distinct functions in centriole biogenesis. SAS-6 assembles to the cartwheel (2, 3) and BLD10/CEP135 forms the pinhead that connects the cartwheel spokes to the A-microtubules of the microtubule triplets (4, 5), whereas SAS-4/CPAP controls the elongation of centriolar microtubules (6 -9).Trypanosoma brucei, a flagellated protozoan and the causative agent of human sleeping sickness, does not have centrosomes, but it possesses the basal body as its microtubule-organizing center to nucleate the assembly of a motile flagellum. The basal body is characterized by an array of nine microtubule triplets, with the conserved SAS-6 protein forming the cartwheel structure (10), similar to that of the centrosome in metazoa. The flagellum is attached, along most of its length, to the cell body via a specialized cytoskeletal structure termed the flagellum attachment zone (FAZ), 2 which consists of three main domains: the structure connecting the paraflagellar rod (PFR) to the flagellar membrane, the structure connecting the flagellar membrane and the cell body membrane, and a cytoplasmic filament (often referred to as the FAZ filament) and its associated microtubule quartet (11)(12)(13)(14)(15)(16)(17). In addition to mediating flagellum-cell body attachment, the FAZ filament also defines the cytokinesis cleavage plane (11,12), with the distal tip of the new FAZ filament marking the site of cytokinesis initiation (18 -20). Moreover, during the cell cycle in the procyclic form, the elongation of the FAZ filament positions the newly assembled basal body toward the cell posterior (21), which is crucial for organelle segregation and cell division (10,(22)(23)(24)(25).Trypanosomatids, a group of kinetoplastid parasites consisting of T. brucei, Trypanosoma cruzi, and Leishmania spp., appear in a variety of different morphological forms during their life cycle and are distinguished by the relative position of the kinetoplast (mitochondrial DNA) and the nucleus and by the position, length, and cell body attachment of the flagellum (26). In the tsetse fly vector, T. brucei differentiates from the trypomastigote form to the epimastigote form, which undergoes asymmetrical cell division to produce a long epimastigote cell and a short epimastigote cell (26). How life cycle transitions in T. brucei are regulated is largely unknown, but recent work has begun to uncover the regulators involved in this process. ALBA3 and ALBA4, two closed related RNA-binding proteins, are the first factors found to be involved in life cycle transitions in T. brucei (27). Anothe...

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“…Alba3 has also been shown to be a component of a multiprotein complex engaged in the storage of translationally silent mRNAs that is critical for zygote to ookinete transformation [29]. Similarly, it is a component of Trypanosoma brucei RNA granules associated with starvation stress and trypanosome differentiation [30] [31]. Specifically, Subota et al demonstrated that overexpression of Alba3 perturbs differentiation of T .…”

Section: Resultsmentioning

confidence: 99%

“…Overexpression of Alba3 in T . brucei , the protozoan parasite that causes sleeping sickness, impairs differentiation of the trypanosome in the tsetse fly [31]. Pf .…”

Section: Discussionmentioning

confidence: 99%

Molecular Markers of Radiation Induced Attenuation in Intrahepatic Plasmodium falciparum Parasites

et al. 2016

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Experimental immunization with radiation attenuated sporozoites (RAS) and genetically attenuated sporozoites has proved to be a promising approach for malaria vaccine development. However, parasite biomarkers of growth attenuation and enhanced immune protection in response to radiation remain poorly understood. Here, we report on the effect of an attenuating dose of γ-irradiation (15 krad) on the Plasmodium falciparum sporozoite (PfSPZ) ultrastructure by electron microscopy, growth rate of liver stage P. falciparum in liver cell cultures, and genome-wide transcriptional profile of liver stage parasites by microarray. We find that γ-irradiation treated PfSPZ retained a normal cellular structure except that they were vacuous with a partially disrupted plasma membrane and inner membrane complex. A similar infection rate was observed by γ-irradiation-treated and untreated PfSPZ in human HCO-4 liver cells (0.47% versus 0.49%, respectively) on day 3 post-infection. In the microarray studies, cumulatively, 180 liver stage parasite genes were significantly transcriptionally altered on day 3 and/or 6 post-infection. Among the transcriptionally altered biomarkers, we identified a signature of seven candidate parasite genes that associated with functionally diverse pathways that may regulate radiation induced cell cycle arrest of the parasite within the hepatocyte. A repertoire of 14 genes associated with protein translation is transcriptionally overexpressed within the parasite by radiation. Additionally, 37 genes encode proteins expressed on the cell surface or exported into the host cell, 4 encode membrane associated transporters, and 10 encode proteins related to misfolding and stress-related protein processing. These results have significantly increased the repertoire of novel targets for 1) biomarkers of safety to define proper attenuation, 2) generating genetically attenuated parasite vaccine candidates, and 3) subunit candidate vaccines against liver stage malaria.

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ALBA proteins are stage regulated during trypanosome development in the tsetse fly and participate in differentiation

Cited by 94 publications

References 67 publications

Forward motility is essential for trypanosome infection in the tsetse fly

Forward motility is essential for trypanosome infection in the tsetse fly

SAS-4 Protein in Trypanosoma brucei Controls Life Cycle Transitions by Modulating the Length of the Flagellum Attachment Zone Filament

Molecular Markers of Radiation Induced Attenuation in Intrahepatic Plasmodium falciparum Parasites

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