Cold shock and regulation of surface protein trafficking convey sensitization to inducers of stage differentiation in <i>Trypanosoma brucei</i>

Engstler, Markus; Boshart, Michael

doi:10.1101/gad.323404

Cited by 169 publications

(224 citation statements)

References 76 publications

(105 reference statements)

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“…To assess the differentiation process, we monitored the developmental expression of the surface glycoproteins by double immunofluorescence using anti-procyclin and anti-VSG221 antibodies. Importantly, cold shock at 20°C was not carried out to avoid premature procyclin expression; thus procyclin expression is driven by the availability of cisaconitate and the sensitivity of the trypanosome to this metabolite (30). The procyclic form obtained after TbTOR4 depletion consistently was maintained for longer periods than in control cells.…”

Section: Methodsmentioning

confidence: 99%

Third target of rapamycin complex negatively regulates development of quiescence in Trypanosoma brucei

Barquilla

Saldivia

Díaz

et al. 2012

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

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African trypanosomes are protozoan parasites transmitted by a tsetse fly vector to a mammalian host. The life cycle includes highly proliferative forms and quiescent forms, the latter being adapted to host transmission. The signaling pathways controlling the developmental switch between the two forms remain unknown. Trypanosoma brucei contains two target of rapamycin (TOR) kinases, TbTOR1 and TbTOR2, and two TOR complexes, TbTORC1 and TbTORC2. Surprisingly, two additional TOR kinases are encoded in the T. brucei genome. We report that TbTOR4 associates with an Armadillo domain-containing protein (TbArmtor), a major vault protein, and LST8 to form a unique TOR complex, TbTORC4. Depletion of TbTOR4 caused irreversible differentiation of the parasite into the quiescent form. AMP and hydrolysable analogs of cAMP inhibited TbTOR4 expression and induced the stumpy quiescent form. Our results reveal unexpected complexity in TOR signaling and show that TbTORC4 negatively regulates differentiation of the proliferative form into the quiescent form.parasitology | cell biology | kinetoplastida

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Section: Methodsmentioning

confidence: 99%

Third target of rapamycin complex negatively regulates development of quiescence in Trypanosoma brucei

Barquilla

Saldivia

Díaz

et al. 2012

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

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“…brucei AnTat 1.1 E , a pleomorphic clone, derived from an EATRO1125 clone was originally isolated from blood of Tragelaphus scriptus in Uganda. For all the experiments, we used AnTat 1.1 E 90-13, a transgenic cell-line encoding the tetracyclin repressor and T7 RNA polymerase 34 .…”

Section: Parasites and Culture Conditionsmentioning

confidence: 99%

Trypanosoma brucei metabolism is under circadian control

et al. 2017

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TX 75390-9111, USAThe Earth's rotation forced life to evolve under cyclic day and night environmental changes. In order to anticipate such daily cycles, prokaryote and eukaryote free-living organisms evolved intrinsic clocks that regulate physiological and behavioral processes. Daily rhythms have been observed in organisms living within hosts, such as parasites. Whether parasites have intrinsic molecular clocks or whether they simply respond to host rhythmic physiological cues remains unknown. Here we show that Trypanosoma brucei, the causative agent of human sleeping sickness, has an intrinsic circadian clock that regulates its metabolism in two different stages of the life cycle. We found that in vitro approximately 10% of genes in T. brucei are expressed with a circadian rhythm. The maximum expression of these genes occurs at two different phases of the day and may depend on a posttranscriptional mechanism. Circadian genes are enriched in cellular metabolic pathways, and coincide with two peaks of intracellular ATP concentration. Moreover, daily changes in the parasite population lead to differences in suramin sensitivity, a drug commonly used to treat Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature

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“…pG-⌬164.EG derivative pG-M1.5 (38) 5 that had been cut with XbaI, treated with Klenow enzyme, and cut with StuI. The resulting plasmid, pGbsr-M1.5, was processed with HindIII and StuI, and the insert was ligated to pTSARib (39) cut with HindIII and EheI, yielding construct pTSA-Ribsr.…”

Section: In Vivo Labeling and Immunoprecipitation-procyclicmentioning

confidence: 99%

“…The resulting plasmid, pGbsr-M1.5, was processed with HindIII and StuI, and the insert was ligated to pTSARib (39) cut with HindIII and EheI, yielding construct pTSA-Ribsr. The EP1-GFP cassette was released from pG-⌬LII.EY (38) by restriction with NdeI, treatment with Klenow enzyme, and restriction with HindIII. The insert was ligated to pTSA-Ribsr cut with BamHI, treated with Klenow enzyme, and cut with HindIII.…”

Section: In Vivo Labeling and Immunoprecipitation-procyclicmentioning

confidence: 99%

Role of Protein Translocation Pathways across the Endoplasmic Reticulum in Trypanosoma brucei

Goldshmidt

Sheiner

Bütikofer

et al. 2008

Journal of Biological Chemistry

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The translocation of secretory and membrane proteins across the endoplasmic reticulum (ER) membrane is mediated by co-translational (via the signal recognition particle (SRP)) and post-translational mechanisms. In this study, we investigated the relative contributions of these two pathways in trypanosomes. A homologue of SEC71, which functions in the post-translocation chaperone pathway in yeast, was identified and silenced by RNA interference. This factor is essential for parasite viability. In SEC71-silenced cells, signal peptide (SP)-containing proteins traversed the ER, but several were mislocalized, whereas polytopic membrane protein biogenesis was unaffected. Surprisingly trypanosomes can interchangeably utilize two of the pathways to translocate SPcontaining proteins except for glycosylphosphatidylinositol-anchored proteins, whose level was reduced in SEC71-silenced cells but not in cells depleted for SRP68, an SRP-binding protein. Entry of SP-containing proteins to the ER was significantly blocked only in cells co-silenced for the two translocation pathways (SEC71 and SRP68). SEC63, a factor essential for both translocation pathways in yeast, was identified and silenced by RNA interference. SEC63 silencing affected entry to the ER of both SP-containing proteins and polytopic membrane proteins, suggesting that, as in yeast, this factor is essential for both translocation pathways in vivo. This study suggests that, unlike bacteria or other eukaryotes, trypanosomes are generally promiscuous in their choice of mechanism for translocating SPcontaining proteins to the ER, although the SRP-independent pathway is favored for glycosylphosphatidylinositol-anchored proteins, which are the most abundant surface proteins in these parasites.

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Cold shock and regulation of surface protein trafficking convey sensitization to inducers of stage differentiation in Trypanosoma brucei

Abstract: [Keywords: GPI-anchor; post-transcriptional; procyclin; protein sorting; thermoregulation; tsetse] Supplemental material is available at http://www.genesdev.org.

Cited by 169 publications

References 76 publications

Third target of rapamycin complex negatively regulates development of quiescence in Trypanosoma brucei

Third target of rapamycin complex negatively regulates development of quiescence in Trypanosoma brucei

Trypanosoma brucei metabolism is under circadian control

Role of Protein Translocation Pathways across the Endoplasmic Reticulum in Trypanosoma brucei

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