Control of gene expression in Trypanosomatidae

Teixeira, Santuza Maria Ribeiro

doi:10.1590/s0100-879x1998001200001

Cited by 75 publications

(53 citation statements)

References 58 publications

(66 reference statements)

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“…probably proceeds unidirectionally (Myler et al, 1999) and is mostly constitutive: gene expression is regulated at the levels of RNA processing, RNA stability, and/or translation control (Curotto de Lafaille et al, 1992;Aly et al, 1994;Brandau et al, 1995;Graham, 1995;Teixeira, 1998;Stiles et al, 1999). Nevertheless, Hsp90 can obviously chaperone the factors involved at these levels of regulation as well.…”

Section: A Role For Hsp90 In Posttranscriptional Stress Responsementioning

confidence: 99%

Heat Shock Protein 90 Homeostasis Controls Stage Differentiation in Leishmania donovani

Wiesgigl

Clos

2001

MBoC

185

174

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The differentiation of Leishmania parasites from the insect stage, the promastigote, toward the pathogenic mammalian stage, the amastigote, is triggered primarily by the rise in ambient temperature encountered during the insect-to-mammal transmission. We show here that inactivation of heat shock protein (Hsp) 90, with the use of the drugs geldanamycin or radicicol, mimics transmission and induces the differentiation from the promastigote to the amastigote stage. Geldanamycin also induces a growth arrest of cultured promastigotes that can be forestalled by overexpression of the cytoplasmic Hsp90. Moreover, we demonstrate that Hsp90 serves as a feedback inhibitor of the cellular heat shock response in Leishmania. Our results are consistent with Hsp90 homeostasis serving as cellular thermometer for these primitive eukaryotes, controlling both the heat shock response and morphological differentiation. INTRODUCTIONProtozoan parasites of the genus Leishmania are transmitted by blood-feeding sand flies to mammalian hosts, including humans, whereby they encounter a rise in ambient temperature. Subjecting cultured insect stages, the promastigotes, of various Leishmania species to a similar temperature upshift in vitro results in the transient posttranscriptional upregulation of both heat shock protein (Hsp) 90 (also known as Hsp83) and Hsp70 synthesis and a persistent induction of Hsp100 expression Brandau et al., 1995;Krobitsch et al., 1998). Moreover, species such as L. mexicana, L. pifanoi, and L. donovani will, during heat stress and acidification of the medium, show a morphological transition toward the mammalian stage, the amastigote (Zilberstein and Shapira, 1994;Saar et al., 1998). Such axenic amastigotes are indistinguishable from true host tissue-derived intracellular amastigotes (Bates, 1993;Pan et al., 1993;Charest and Matlashewski, 1994;Charest et al., 1996;Gupta et al., 1996;Saar et al., 1998). Thus, the rise of temperature encountered during transmission can be viewed not as stress but rather as signal for cellular differentiation.We have shown previously that Hsp100 is critical for the expression of some amastigote stage-specific proteins and for overall virulence of the parasites (Hubel et al., 1997;Krobitsch et al., 1998); however, gene replacement mutants lacking Hsp100 still show, induced by elevated temperature, morphological differentiation to viable amastigote-like culture stages, indicating that the induction of morphological differentiation occurs independently or upstream of Hsp100 (Krobitsch et al., 1998;Krobitsch and Clos, 1999).Another chaperone, Hsp90 (Hsp83), is one of the most abundant proteins in Leishmania, constituting 2.8% of the cellular protein . Hsp90 (Hsp83) is encoded by multiple gene copies and is found in the soluble fraction of the cytoplasm (Shapira and Pinelli, 1989;Brandau et al., 1995;Hubel and Clos, 1996). Its sequence is distinct from the Grp94 homologue of L. infantum, which was characterized recently (Larreta et al., 2000). In higher eukaryotes and in yeast, cytosolic H...

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Section: A Role For Hsp90 In Posttranscriptional Stress Responsementioning

confidence: 99%

Heat Shock Protein 90 Homeostasis Controls Stage Differentiation in Leishmania donovani

Wiesgigl

Clos

2001

MBoC

185

174

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“…Notably, even though orthologs for all of the conserved components of the RNA polymerase II complex have been identified in the Tri-Tryp genome (Ivens et al 2005), the transcription of two trypanosomatid genes, variant surface protein and procyclin genes in T. brucei, as well as several exogenous genes that are transfected into T. cruzi, is mediated by RNA polymerase I (Palenchar & Bellofatto 2006). Once the polycistronic pre-mRNA is produced, the following two coupled reactions allow for the generation of mature monocistronic transcripts: trans-splicing and polyadenylation (Teixeira & DaRocha 2003). Every trypanosomatid mature mRNA possesses a SL sequence, which is a capped sequence that contains the same 39 nucleotides on the 5' end, and this SL is attached to the transcript in a process called transsplicing (Liang et al 2003).…”

mentioning

confidence: 99%

Regulatory elements involved in the post-transcriptional control of stage-specific gene expression in Trypanosoma cruzi: a review

Araújo

Teixeira

2011

Mem. Inst. Oswaldo Cruz

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Trypanosoma cruzi is an intracellular parasite that is transmitted by at least 40 different blood-sucking triatomine species to over 1,000 mammalian species (Brener et al. 2000). This parasite must adapt to enormous changes in its extracellular milieu, such as changes in environmental temperature as well as in the available nutrients inside each host. The parasite has a complex life cycle that is characterised by four stages; epimastigotes and metacyclic trypomastigotes are present in the insect vector, whereas intracellular amastigotes and bloodstream trypomastigotes are present in the mammalian host. Thus, this species must develop a broad set of molecular tools that allow it to multiply in the insect gut, to invade and multiply inside a large number of distinct mammalian cell types and to circumvent host immune defence systems. To meet such phenotypic plasticity, T. cruzi relies on unique mechanisms that can control the expression of its repertoire of about 12,000 genes. Because its genome is constitutively transcribed into long polycistronic primary transcripts, mRNAs for proteincoding genes must be processed through trans-splicing and polyadenylation reactions. The mRNAs must also interact with different protein factors in a complex posttranscriptional regulatory machinery that determines the levels of their protein product according to the cellular demands of the parasite in each stage of its life cycle.In the same issue that the T. cruzi genome was published (El-Sayed et al. 2005a), a study describing its proteome was also reported (Atwood et al. 2005). Proteins extracted from whole-cell and subcellular lysates of the four stages of T. cruzi were analysed by mass spectrometry (epimastigotes, metacyclic trypomastigotes, amastigotes and trypomastigotes), which identified 2,784 proteins belonging to the 1,168 protein groups in the annotated T. cruzi genome. Although about 30% of the identified proteins were found at all life-cycle stages, at least 248 proteins were only expressed at one stage, thereby demonstrating significant changes in the relative abundance of T. cruzi proteins throughout its life cycle. One of the main findings in these proteomic analyses was that the four parasite stages use distinct energy sources (Atwood et al. 2005); intracellular amastigotes upregulated proteins involved in lipid-dependent energy metabolism, such as enzymes of the citric acid cycle, whereas enzymes capable of catalysing the conversion of histidine to glutamate were more abundant in the insect epimastigote stage. Heat-shock proteins (HSP) and proteins involved in vesicular trafficking were also preferentially detected in amastigotes. Furthermore, enzymes involved in antioxidant defence were upregulated during the transformation of epimastigotes into invasive metacyclic trypomastigotes, whereas bloodstream trypomastigotes upregulated the surface expression of several large gene families that are known to be involved in interacting with the mammalian host (Atwood et al. 2005).In agreement with this proteomics data, glo...

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“…We chose to analyze only the polysome-associated mRNA fraction because gene expression in T. cruzi is predominantly regulated at the posttranscriptional level (Teixeira 1998, Clayton 2002. The mechanisms thought to be involved in regulating T. cruzi gene expression determine mRNA half-life and accessibility to the translation machinery , da Silva et al 2006.…”

Section: Discussionmentioning

confidence: 99%

Characterization of TcSTI-1, a homologue of stress-induced protein-1, in Trypanosoma cruzi

Schmidt

Soares

Goldenberg

et al. 2011

Mem. Inst. Oswaldo Cruz

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Key words: STI-1 -Hop -HSP70 -stress response -Trypanosoma cruziThe stress-induced protein-1 (STI-1), also known as Hop (HSP70/HSP90-organising protein), is a co-chaperone that interacts with the heat-shock proteins HSP70 and HSP90 (Smith et al. 1993). This multi-chaperone complex is required for steroid receptor (SR) assembly (Chen et al. 1996, Dittmar et al. 1996, Chang et al. 1997 in which STI-1 acts as a mediator, potentially increasing the rate of SR maturation (Morishima et al. 2000). Furthermore, this chaperone complex is able to reconstitute hepadnavirus reverse transcriptase activity in vitro (Hu et al. 2002), suggesting that a purified assembly system could be used to mediate various biological processes requiring HSP90 function (Pratt & Toft 2003).STI-1 acts as an adaptor protein, mediating the interaction between HSP70 and HSP90 through its tetratricopeptide repeat (TPR) domains. The N-terminal TPR domain (TPR1) specifically recognizes the C-terminus of HSP70, whereas the central TPR domain (TPR2A) binds the C-terminus of HSP90 (Chen & Smith 1998, Scheufler et al. 2000. The C-terminal domain of STI-1 seems to be involved in the interactions with both HSPs (Flom et al. 2007, Onuoha et al. 2008. STI-1 may also modulate HSP activities (Johnson et al. 1998, Richter et al. 2003, Odunuga et al. 2004). The STI-1 gene was first isolated and characterized in Saccharomyces cerevisiae during a genetic screen for proteins involved in the heat-shock response. The gene was named "stress-inducible" because, like other wellcharacterized HSP genes, it was induced by heat shock and by the arginine analogue canavanine. However, the nucleotide sequence of STI-1 displayed no similarity to the sequences of other HSP-encoding genes (Nicolet & Craig 1989). Like their counterpart in yeast, the mouse and Caenorhabditis elegans STI-1 homologues are induced by heat shock (Lässle et al. 1997, Song et al. 2009). Interestingly, a soybean homologue has been shown to be induced by either heat or cold stress (Zhang et al. 2003). In addition, the upregulation of STI-1 observed in human SV-40-transformed fibroblasts or mouse macrophages exposed to bacterial lipopolysaccharide demonstrates that stress conditions unrelated to temperature may also lead to the induction of STI-1 expression (Honoré et al. 1992, Heine et al. 1999. The murine STI-1 was identified as a cytoplasmic protein (Lässle et al. 1997). However, a small fraction of STI-1 was found bound to a cellular prion protein at the cell membrane, where it promotes neuroprotection against cell death (Zanata et al. 2002). Moreover, STI-1 accumulates in the nucleus of murine fibroblasts after treatment with leptomycin B, a nuclear export inhibitor . A human homologue has also been found in the Golgi apparatus and in small vesicles within fibroblasts (Honoré et al. 1992).A protozoan orthologue of STI-1 has been characterized in Leishmania major and shown to be upregulated when the parasites are exposed to heat stress conditions (Webb et al. 1997). This parasite, like other trypanoso-S...

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Control of gene expression in Trypanosomatidae

Cited by 75 publications

References 58 publications

Heat Shock Protein 90 Homeostasis Controls Stage Differentiation in Leishmania donovani

Heat Shock Protein 90 Homeostasis Controls Stage Differentiation in Leishmania donovani

Regulatory elements involved in the post-transcriptional control of stage-specific gene expression in Trypanosoma cruzi: a review

Characterization of TcSTI-1, a homologue of stress-induced protein-1, in Trypanosoma cruzi

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