Confocal microscopic investigation of tubulin distribution and effect of paclitaxel on posttranslationally modified tubulins in sodium arsenite resistant Leishmania donovani

Chavan, Hemantkumar; Singh, Gaganmeet; Dey, Chinmoy Sankar

doi:10.1016/j.exppara.2007.01.016

Cited by 12 publications

(10 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The ability of YL 1/2 to label multiple microtubule-based structures in Leishmania mexicana is similar to observations of a previous study employing another antibody directed against tyrosinated α -tubulin in which broad labeling of L . donovani microtubule containing structures was observed [ 27 ]. In contrast, two other antibodies directed against untryosinated α -tubulin (rabbit or mouse anti- α -tubulin, Sigma) did not efficiently label the amastigote flagellum (not shown), providing a compelling pragmatic reason to use the YL1/2 antibody instead.…”

Section: Resultsmentioning

confidence: 99%

Kharon1 Null Mutants of Leishmania mexicana Are Avirulent in Mice and Exhibit a Cytokinesis Defect within Macrophages

et al. 2015

View full text Add to dashboard Cite

In a variety of eukaryotes, flagella play important roles both in motility and as sensory organelles that monitor the extracellular environment. In the parasitic protozoan Leishmania mexicana, one glucose transporter isoform, LmxGT1, is targeted selectively to the flagellar membrane where it appears to play a role in glucose sensing. Trafficking of LmxGT1 to the flagellar membrane is dependent upon interaction with the KHARON1 protein that is located at the base of the flagellar axoneme. Remarkably, while Δ kharon1 null mutants are viable as insect stage promastigotes, they are unable to survive as amastigotes inside host macrophages. Although Δ kharon1 promastigotes enter macrophages and transform into amastigotes, these intracellular parasites are unable to execute cytokinesis and form multinucleate cells before dying. Notably, extracellular axenic amastigotes of Δ kharon1 mutants replicate and divide normally, indicating a defect in the mutants that is only exhibited in the intra-macrophage environment. Although the flagella of Δ kharon1 amastigotes adhere to the phagolysomal membrane of host macrophages, the morphology of the mutant flagella is often distorted. Additionally, these null mutants are completely avirulent following injection into BALB/c mice, underscoring the critical role of the KHARON1 protein for viability of intracellular amastigotes and disease in the animal model of leishmaniasis.

show abstract

Section: Resultsmentioning

confidence: 99%

Kharon1 Null Mutants of Leishmania mexicana Are Avirulent in Mice and Exhibit a Cytokinesis Defect within Macrophages

et al. 2015

View full text Add to dashboard Cite

show abstract

“…For this reason tubulin peptides identified were examined for the presence of post‐translational modifications. Tubulins display a variety of post‐translational modifications such as glutamylation (α and β tubulin subunits), acetylation and tyrosination (α tubulin subunit) (Kohl and Gull, ; Chavan et al ., ), phosphorylation (Prasad and Dey, ; Rosenzweig et al ., ) and glycosylation (Rosenzweig et al ., ). Although in our analysis we searched for the pre‐mentioned modifications, we were not able to identify any.…”

Section: Resultsmentioning

confidence: 99%

The loss of virulence of histone H1 overexpressing Leishmania donovani parasites is directly associated with a reduction of HSP83 rate of translation

Alexandratos

Clos

Samiotaki

et al. 2013

Molecular Microbiology

View full text Add to dashboard Cite

SummaryOverexpression of Leishmania histone H1 (LeishH1) was previously found to cause a promastigote-toamastigote differentiation handicap, deregulation of cell-cycle progression, and loss of parasite infectivity. The aim of this study was to identify changes in the proteome of LeishH1 overexpressing parasites associated with the avirulent phenotype observed. 2D-gel electrophoresis analysis revealed only a small protein subset of differentially expressed proteins in the LeishH1 overexpressing promastigotes. Among these was the chaperone HSP83, known for its protective role in Leishmania drug-induced apoptosis, which displayed lower translational rates. To investigate if the lower expression levels of HSP83 are associated with the differentiation handicap, we assayed the thermostability of parasites by subjecting them to heat-shock (25°C→37°C), a natural stress-factor occurring during stage differentiation. Heat-shock promoted apoptosis to a greater extent in the LeishH1 overexpressing parasites. Interestingly, these parasites were not only more sensitive to heat-shock but also to drug-induced [Sb(III)] cell-death. In addition, the restoration of HSP83 levels re-established drug resistance, and restored infectivity to LeishH1 overexpressing parasites in the murine J774 macrophage model. Overall, this study suggests that LeishH1 levels are critical for the parasite's stress-induced adaptation within the mammalian host, and highlights the cross-talk between pathways involved in drug resistance, apoptosis and virulence.

show abstract

“…In Tritryps acetylated α -tubulin is found in the subpellicular microtubules that run along the inner surface of the parasites. This array of MT plays an essential role in the maintenance of the parasites shape and is remodelled during the differentiation process throughout its life cycle [60–62]. This PTM is also present in the axoneme of the flagellum and in the ephemeral microtubules of the mitotic spindle of T. brucei [63].…”

Section: Acetylation: a General Posttranslational Modificationmentioning

confidence: 99%

Lysine Acetylation: Elucidating the Components of an Emerging Global Signaling Pathway in Trypanosomes

Alonso

Serra

2012

Journal of Biomedicine and Biotechnology

View full text Add to dashboard Cite

In the past ten years the number of acetylated proteins reported in literature grew exponentially. Several authors have proposed that acetylation might be a key component in most eukaryotic signaling pathways, as important as phosphorylation. The enzymes involved in this process are starting to emerge; acetyltransferases and deacetylases are found inside and outside the nuclear compartment and have different regulatory functions. In trypanosomatids several of these enzymes have been described and are postulated to be novel antiparasitic targets for the rational design of drugs. In this paper we overview the most important known acetylated proteins and the advances made in the identification of new acetylated proteins using high-resolution mass spectrometry. Also, we summarize what is known so far about the acetyltransferases and deacetylases in eukaryotes, focusing on trypanosomes and their potential use as chemotherapeutic targets.

show abstract

Confocal microscopic investigation of tubulin distribution and effect of paclitaxel on posttranslationally modified tubulins in sodium arsenite resistant Leishmania donovani

Cited by 12 publications

References 38 publications

Kharon1 Null Mutants of Leishmania mexicana Are Avirulent in Mice and Exhibit a Cytokinesis Defect within Macrophages

Kharon1 Null Mutants of Leishmania mexicana Are Avirulent in Mice and Exhibit a Cytokinesis Defect within Macrophages

The loss of virulence of histone H1 overexpressing Leishmania donovani parasites is directly associated with a reduction of HSP83 rate of translation

Lysine Acetylation: Elucidating the Components of an Emerging Global Signaling Pathway in Trypanosomes

Contact Info

Product

Resources

About