Distinct Roles of a Mitogen-Activated Protein Kinase in Cytokinesis between Different Life Cycle Forms of Trypanosoma brucei

Wei, Ying; Li, Ziyin

doi:10.1128/ec.00258-13

Cited by 12 publications

(11 citation statements)

References 57 publications

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“…Our work that knockdown of TbCentrin3 or TbIAD5‐1 disrupted the localization of multiple cytokinesis regulators to the cytokinesis initiation site (Figs and ) provided, for the first time, some molecular insights into the flagellar protein‐mediated control of cytokinesis initiation in the bloodstream form. Although there are substantial differences in cell cycle control between the procyclic form and the bloodstream form (Hammarton et al , ; Tu and Wang, ; Li and Wang, ; Wheeler et al , ; Wei and Li, ; Zhang et al , ), we found that those cytokinesis regulators essential for cytokinesis initiation in the procyclic form have similar subcellular localizations and functions in the bloodstream form (Zhang et al , ). The cytokinesis initiation site in both the procyclic form and the bloodstream form appears to be similarly located at a region close to the new FAZ tip, where the cytokinesis initiation regulators CIF1, CIF2, and CIF3 are all localized (Zhou et al , ; ; Kurasawa et al , ; Zhang et al , ).…”

Section: Discussionmentioning

confidence: 51%

Functional analyses of an axonemal inner‐arm dynein complex in the bloodstream form of Trypanosoma brucei uncover its essential role in cytokinesis initiation

Zhang

Lun

et al. 2019

Molecular Microbiology

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Summary The flagellated eukaryote Trypanosoma brucei alternates between the insect vector and the mammalian host and proliferates through an unusual mode of cell division. Cell division requires flagellum motility‐generated forces, but flagellum motility exerts distinct effects between different life cycle forms. Motility is required for the final cell abscission of the procyclic form in the insect vector, but is necessary for the initiation of cell division of the bloodstream form in the mammalian host. The underlying mechanisms remain elusive. Here we carried out functional analyses of a flagellar axonemal inner‐arm dynein complex in the bloodstream form and investigated its mechanistic role in cytokinesis initiation. We showed that the axonemal inner‐arm dynein heavy chain TbIAD5‐1 and TbCentrin3 form a complex, localize to the flagellum, and are required for viability in the bloodstream form. We further demonstrated the interdependence between TbIAD5‐1 and TbCentrin3 for maintenance of protein stability. Finally, we showed that depletion of TbIAD5‐1 and TbCentrin3 arrested cytokinesis initiation and disrupted the localization of multiple cytokinesis initiation regulators. These findings identified the essential role of an axonemal inner‐arm dynein complex in cell division, and provided molecular insights into the flagellum motility‐mediated cytokinesis initiation in the bloodstream form of T. brucei.

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Section: Discussionmentioning

confidence: 51%

Functional analyses of an axonemal inner‐arm dynein complex in the bloodstream form of Trypanosoma brucei uncover its essential role in cytokinesis initiation

Zhang

Lun

et al. 2019

Molecular Microbiology

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“…The T. brucei genome contains between 176 – 182 putative protein kinases (PKs) [42, 43], and our data contains 18 phosphorylation sites on 14 PKs that alter significantly in response to heat shock (Table 2), whilst no PKs change significantly at the protein level. PKs with HS sensitive phosphorylation sites include many that have been demonstrated to be essential, and where RNAi ablation in the bloodstream form causes a cell cycle defect, including CK1.2, GSK3, MAPK6, PLK, RCK [52–55]. Amongst the 18 significantly regulated phosphorylation sites, 8 sites decrease in abundance upon HS including the essential AGC S229 (3.2-fold), PLK T198 (3.6-fold) and CDK2 Y57 (3.6-fold).…”

Section: Resultsmentioning

confidence: 99%

Phosphoproteomic analysis of mammalian infectiveTrypanosoma bruceisubjected to heat shock suggests atypical mechanisms for thermotolerance

Ooi

Benz

Urbaniak

2020

Preprint

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The symptoms of African sleeping sickness, caused by the parasite Trypanosoma brucei, can include periods of fever as high as 41 °C which triggers a heat shock response in the parasite. To capture events involved in sensing and responding to heat shock in the mammalian infective form we have conducted a SILAC-based quantitative proteomic and phosphoproteomic analysis of T. brucei cells treated at 41 °C for 1h. Our analysis identified 193 heat shock responsive phosphorylation sites with an average of 5-fold change in abundance, but only 20 heat shock responsive proteins with average of 1.5-fold change. These data indicate that protein abundance does not rapidly respond (≤1 h) to heat shock, and that the changes observed in phosphorylation site abundance are larger and more widespread. The heat shock responsive phosphorylation sites showed enrichment of RNA binding proteins with putative roles in heat shock response included P-body / stress granules and the eukaryotic translation initiation 4F complex. The ZC3H11-MKT1 complex, which stabilises mRNAs of thermotolerance proteins, appears to represent a key signal integration node in the heat shock response.

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“…Two PKs show a very distinct peak in phosphorylation site abundance at a single time point; MAPK6 pY176 (FCMax 4-fold) and RCK pS344 (FCMax 9-fold) that both peak at the EG2M only ( Figure 5E & F) and belong to Cluster 883 (24 members). Ablation of either MAPK6 or RCK by RNAi results in a cytokinesis defect in bloodstream form parasites (27), and ablation of MAPK6 in the procyclic form results in a cytokinesis defect related to stalled furrow ingression (29). These results suggest that these phosphorylation sites may be required to complete cytokinesis.…”

Section: Cell Cycle Regulation Of Protein Kinasesmentioning

confidence: 93%

“…The T. brucei genome contains between 176 -182 putative protein kinases (PKs) (25, 26), and our data contains 54 CCR phosphorylation sites (average FCMax 5-fold) on 37 PKs, with 12 PKs CCR at the protein level (average FCMax 2-fold) (Supplemental Figure S4). PKs with CCR phosphorylation sites include many that have been demonstrated to be essential, and where RNAi ablation in the bloodstream form results in a cell cycle defect, including CLK1/KKT10, CRK3, KKT3, MAPK6, PK50, PLK, RCK, TOR4, TLK2 and WEE1 (27)(28)(29). In addition the data set contains 8 CCR phosphorylation sites (average FCMax 10-fold) on 3 cyclins, and 3 cyclins are CCR at the protein level (average FCMax of 2-fold).…”

Section: Cell Cycle Regulation Of Protein Kinasesmentioning

confidence: 99%

Organising the cell cycle in the absence of transcriptional control: Dynamic phosphorylation co-ordinates theTrypanosoma bruceicell cycle post-transcriptionally

Benz

Urbaniak

2019

Preprint

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The cell division cycle of the unicellular eukaryote Trypanosome brucei is tightly regulated despite the paucity of transcriptional control that results from the arrangement of genes in polycistronic units and lack of dynamically regulated transcription factors. To identify the contribution of dynamic phosphorylation to T. brucei cell cycle control we have combined cell cycle synchronisation by centrifugal elutriation with quantitative phosphoproteomic analysis. Cell cycle regulated changes in phosphorylation site abundance (917 sites, average 5-fold change) were more widespread and of a larger magnitude than changes in protein abundance (443 proteins, average 2-fold change) and were mostly independent of each other. Hierarchical clustering of co-regulated phosphorylation sites according to their cell cycle profile revealed that a bulk increase in phosphorylation occurs across the cell cycle, with a significant enrichment of known cell cycle regulators and RNA binding proteins (RBPs) within the largest clusters. Cell cycle regulated changes in essential cell cycle kinases are temporally co-ordinated with differential phosphorylation of components of the kinetochore and eukaryotic initiation factors, along with many RBPs not previously linked to the cell cycle such as eight PSP1-C terminal domain containing proteins. The temporal profiles demonstrate the importance of dynamic phosphorylation in co-ordinating progression through the cell cycle, and provide evidence that RBPs play a central role in post-transcriptional regulation of the T. brucei cell cycle.Data are available via ProteomeXchange with identifier PXD013488.

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Distinct Roles of a Mitogen-Activated Protein Kinase in Cytokinesis between Different Life Cycle Forms of Trypanosoma brucei

Cited by 12 publications

References 57 publications

Functional analyses of an axonemal inner‐arm dynein complex in the bloodstream form of Trypanosoma brucei uncover its essential role in cytokinesis initiation

Functional analyses of an axonemal inner‐arm dynein complex in the bloodstream form of Trypanosoma brucei uncover its essential role in cytokinesis initiation

Phosphoproteomic analysis of mammalian infectiveTrypanosoma bruceisubjected to heat shock suggests atypical mechanisms for thermotolerance

Organising the cell cycle in the absence of transcriptional control: Dynamic phosphorylation co-ordinates theTrypanosoma bruceicell cycle post-transcriptionally

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