A novel phosphatase cascade regulates differentiation in <i>Trypanosoma brucei</i> via a glycosomal signaling pathway

Szöőr, Balázs; Burchmore, Richard; Matthews, Keith R.

doi:10.1101/gad.570310

Cited by 118 publications

(143 citation statements)

References 51 publications

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“…CCA also appears to affect the activity of Tb PTP1, a phosphotyrosine phosphatase, which prevents the development from stumpy to procyclic forms [41]. A downstream substrate for Tb PTP1 is a glycosomal directed serine/threonine-specific phosphatase, Tb PIP39, which promotes differentiation when it becomes phosphorylated as a consequence of the inhibition of Tb PTP1 [42]. Intriguingly, whereas PAD1, PAD2, PAD3, PAD5 and PAD7 were down-regulated between 3.9- and 6.2-fold in the proventriculus transcriptome when compared to that of the midgut, PAD4, PAD6 and PAD8 were 5.4-, 6.0- and 4.5-fold up-regulated, respectively, in trypanosomes residing in salivary glands when compared to the proventriculus transcriptome (S1 Table).…”

Section: Resultsmentioning

confidence: 99%

Transcriptome Profiling of Trypanosoma brucei Development in the Tsetse Fly Vector Glossina morsitans

et al. 2016

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African trypanosomes, the causative agents of sleeping sickness in humans and nagana in animals, have a complex digenetic life cycle between a mammalian host and an insect vector, the blood-feeding tsetse fly. Although the importance of the insect vector to transmit the disease was first realized over a century ago, many aspects of trypanosome development in tsetse have not progressed beyond a morphological analysis, mainly due to considerable challenges to obtain sufficient material for molecular studies. Here, we used high-throughput RNA-Sequencing (RNA-Seq) to profile Trypanosoma brucei transcript levels in three distinct tissues of the tsetse fly, namely the midgut, proventriculus and salivary glands. Consistent with current knowledge and providing a proof of principle, transcripts coding for procyclin isoforms and several components of the cytochrome oxidase complex were highly up-regulated in the midgut transcriptome, whereas transcripts encoding metacyclic VSGs (mVSGs) and the surface coat protein brucei alanine rich protein or BARP were extremely up-regulated in the salivary gland transcriptome. Gene ontology analysis also supported the up-regulation of biological processes such as DNA metabolism and DNA replication in the proventriculus transcriptome and major changes in signal transduction and cyclic nucleotide metabolism in the salivary gland transcriptome. Our data highlight a small repertoire of expressed mVSGs and potential signaling pathways involving receptor-type adenylate cyclases and members of a surface carboxylate transporter family, called PADs (Proteins Associated with Differentiation), to cope with the changing environment, as well as RNA-binding proteins as a possible global regulators of gene expression.

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Section: Resultsmentioning

confidence: 99%

Transcriptome Profiling of Trypanosoma brucei Development in the Tsetse Fly Vector Glossina morsitans

et al. 2016

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“…Among the stumpy-enriched transcripts were several that affect transmission to the tsetse stage of the infection. These include MSP-B ( Tb 927.8.1640), required for VSG release upon differentiation, PSSA-2 ( Tb 927.10.11220) and Tb PIP39 ( Tb 09.160.4460), required for recognition of the CCA differentiation signal [34]. In common with intermediate cells, there are nucleolar-associated transcripts that are enriched that may be involved in quiescence (NOG1 Tb 11.02.0620).…”

Section: Resultsmentioning

confidence: 99%

Regulation of Trypanosoma brucei Total and Polysomal mRNA during Development within Its Mammalian Host

et al. 2013

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The gene expression of Trypanosoma brucei has been examined extensively in the blood of mammalian hosts and in forms found in the midgut of its arthropod vector, the tsetse fly. However, trypanosomes also undergo development within the mammalian bloodstream as they progress from morphologically ‘slender forms’ to transmissible ‘stumpy forms’ through morphological intermediates. This transition is temporally progressive within the first wave of parasitaemia such that gene expression can be monitored in relatively pure slender and stumpy populations as well as during the progression between these extremes. The development also represents the progression of cells from translationally active forms adapted for proliferation in the host to translationally quiescent forms, adapted for transmission. We have used metabolic labelling to quantitate translational activity in slender forms, stumpy forms and in forms undergoing early differentiation to procyclic forms in vitro. Thereafter we have examined the cohort of total mRNAs that are enriched throughout development in the mammalian bloodstream (slender, intermediate and stumpy forms), irrespective of strain, revealing those that exhibit consistent developmental regulation rather than sample specific changes. Transcripts that cosediment with polysomes in stumpy forms and slender forms have also been enriched to identify transcripts that escape translational repression prior to transmission. Combined, the expression and polysomal association of transcripts as trypanosomes undergo development in the mammalian bloodstream have been defined, providing a resource for trypanosome researchers. This facilitates the identification of those that undergo developmental regulation in the bloodstream and therefore those likely to have a role in the survival and capacity for transmission of stumpy forms.

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“…Signaling molecules are generated by metabolic process in peroxisomes (Nyathi and Baker, 2006; Joo et al, 2010; Del Rio, 2011), which can modulate the activity of key signaling proteins (Li et al, 2000). Signaling proteins are also targeted directly into peroxisomes, where they integrate external signals to trigger specific cell developmental responses (Szoor et al, 2010). Furthermore, peroxisomes function as a scaffold for the assembly of specific macromolecular signaling complexes, which participate in the orchestration of complex signaling networks (Dixit et al, 2010; Horner et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Peroxisomes and sexual development in fungi

Peraza-Reyes¹,

Berteaux‐Lecellier²

2013

Front. Physiol.

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Peroxisomes are versatile and dynamic organelles that are essential for the development of most eukaryotic organisms. In fungi, many developmental processes, such as sexual development, require the activity of peroxisomes. Sexual reproduction in fungi involves the formation of meiotic-derived sexual spores, often takes place inside multicellular fruiting bodies and requires precise coordination between the differentiation of multiple cell types and the progression of karyogamy and meiosis. Different peroxisomal functions contribute to the orchestration of this complex developmental process. Peroxisomes are required to sustain the formation of fruiting bodies and the maturation and germination of sexual spores. They facilitate the mobilization of reserve compounds via fatty acid β-oxidation and the glyoxylate cycle, allowing the generation of energy and biosynthetic precursors. Additionally, peroxisomes are implicated in the progression of meiotic development. During meiotic development in Podospora anserina, there is a precise modulation of peroxisome assembly and dynamics. This modulation includes changes in peroxisome size, number and localization, and involves a differential activity of the protein-machinery that drives the import of proteins into peroxisomes. Furthermore, karyogamy, entry into meiosis and sorting of meiotic-derived nuclei into sexual spores all require the activity of peroxisomes. These processes rely on different peroxisomal functions and likely depend on different pathways for peroxisome assembly. Indeed, emerging studies support the existence of distinct import channels for peroxisomal proteins that contribute to different developmental stages.

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A novel phosphatase cascade regulates differentiation in Trypanosoma brucei via a glycosomal signaling pathway

Cited by 118 publications

References 51 publications

Transcriptome Profiling of Trypanosoma brucei Development in the Tsetse Fly Vector Glossina morsitans

Transcriptome Profiling of Trypanosoma brucei Development in the Tsetse Fly Vector Glossina morsitans

Regulation of Trypanosoma brucei Total and Polysomal mRNA during Development within Its Mammalian Host

Peroxisomes and sexual development in fungi

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