Dissociation of Cytokinesis Initiation from Mitotic Control in a Eukaryote

Kumar, Praveen; Wang, C. C.

doi:10.1128/ec.5.1.92-102.2006

Cited by 84 publications

(149 citation statements)

References 48 publications

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“…It was previously postulated that TbPLK regulates cytokinesis initiation based on the inhibited growth of the RNAi cells (9,24), but the underlying mechanism has never been addressed. Given that TbPLK disappears from the new FAZ tip before cytokinesis initiation, this raises the question of whether TbPLK plays a direct role in cytokinesis initiation.…”

Section: Discussionmentioning

confidence: 99%

“…As in fungi and metazoa, the Polo-like kinase (TbPLK in T. brucei) and the Aurora B kinase (TbAUK1 in T. brucei) are also required for cytokinesis in T. brucei (9,10). TbPLK is concentrated in the flagellar basal body and the bilobe at late G1 phase, but from early S phase it is concentrated at the new FAZ tip and remains there until early anaphase (11).…”

Section: Trypanosoma Bruceimentioning

confidence: 99%

See 1 more Smart Citation

Two distinct cytokinesis pathways drive trypanosome cell division initiation from opposite cell ends

Zhou¹,

Zhao

et al. 2016

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

160

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Cytokinesis in Trypanosoma brucei, an early branching protozoan, occurs along its longitudinal axis uni-directionally from the anterior tip of the new flagellum attachment zone filament toward the cell's posterior end. However, the underlying mechanisms remain elusive. Here we report that cytokinesis in T. brucei is regulated by a concerted action of Polo-like kinase, Aurora B kinase, and a trypanosome-specific protein CIF1. Phosphorylation of CIF1 by Polo-like kinase targets it to the anterior tip of the new flagellum attachment zone filament, where it subsequently recruits Aurora B kinase to initiate cytokinesis. Consistent with its role, CIF1 depletion inhibits cytokinesis initiation from the anterior end of the cell, but, surprisingly, triggers cytokinesis initiation from the posterior end of the cell, suggesting the activation of an alternative cytokinesis from the opposite cell end. Our results reveal the mechanistic roles of CIF1 and Polo-like kinase in cytokinesis initiation and elucidate the mechanism underlying the recruitment of Aurora B kinase to the cytokinesis initiation site at late anaphase. These findings also delineate a signaling cascade controlling cytokinesis initiation from the anterior end of the cell and uncover a backup cytokinesis that is initiated from the posterior end of the cell when the typical anterior-to-posterior cytokinesis is compromised.cytokinesis | Polo-like kinase | Aurora B kinase | backup cytokinesis |

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Section: Discussionmentioning

confidence: 99%

Section: Trypanosoma Bruceimentioning

confidence: 99%

Two distinct cytokinesis pathways drive trypanosome cell division initiation from opposite cell ends

Zhou¹,

Zhao

et al. 2016

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

160

View full text Add to dashboard Cite

show abstract

“…FAZ1 is conserved amongst kinetoplastids and is required for normal FAZ assembly and flagellum attachment (Vaughan et al, 2008). Intriguingly, given the role of the FAZ in cytokinesis (see section 3.5), it is interesting that a T. brucei polo-like kinase homologue, TbPLK, has been localized to the FAZ (Kumar and Wang, 2006), although a separate study reported that TbPLK localizes to the cytoplasm (Hammarton et al, 2007).…”

Section: Flagellum Attachment Zonementioning

confidence: 99%

The flagellum of Trypanosoma brucei: New tricks from an old dog

Ralston

Hill

2008

International Journal for Parasitology

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African trypanosomes, i.e. Trypanosoma brucei and related sub-species, are devastating human and animal pathogens that cause significant human mortality and limit sustained economic development in sub-Saharan Africa. Trypanosoma brucei is a highly motile protozoan parasite and coordinated motility is central to both disease pathogenesis in the mammalian host and parasite development in the tsetse fly vector. Since motility is critical for parasite development and pathogenesis, understanding unique aspects of the T. brucei flagellum may uncover novel targets for therapeutic intervention in African sleeping sickness. Moreover, studies of conserved features of the T. brucei flagellum are directly relevant to understanding fundamental aspects of flagellum and cilium function in other eukaryotes, making T. brucei an important model system. The T. brucei flagellum contains a canonical 9 + 2 axoneme, together with additional features that are unique to kinetoplastids and a few closely-related organisms. Until recently, much of our knowledge of the structure and function of the trypanosome flagellum was based on analogy and inference from other organisms. There has been an explosion in functional studies in T. brucei in recent years, revealing conserved as well as novel and unexpected structural and functional features of the flagellum. Most notably, the flagellum has been found to be an essential organelle, with critical roles in parasite motility, morphogenesis, cell division and immune evasion. This review highlights recent discoveries on the T. brucei flagellum.

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“…One report indicates that the Polo-like kinase TbPLK localizes to the cleavage furrow in T. brucei (Kumar and Wang, 2006), although a subsequent study suggests that its localization is cytoplasmic (Hammarton et al, 2007). Our phenotype suggests that perturbation of this and other kinases is responsible in part for the defects in kinetoplast and basal body migration (Kumar and Wang, 2006). It is also interesting to note that removal of an autoregulatory domain of the ERK-like, CRKlike protein kinase TbECK1 results in large cells with a DNA content of >4C.…”

Section: Journal Of Cell Science 121 (4)mentioning

confidence: 99%

Sphingolipid synthesis is necessary for kinetoplast segregation and cytokinesis in Trypanosoma brucei

Fridberg

Olson

Nakayasu

et al. 2008

Journal of Cell Science

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Sphingolipids and their metabolites have been thought crucial for cell growth and cell cycle progression, membrane and protein trafficking, signal transduction, and formation of lipid rafts; however, recent studies in trypanosomes point to the dispensability of sphingolipids in some of these processes. In this study, we explore the requirements for de novo sphingolipid biosynthesis in the insect life cycle stage of the African trypanosome Trypanosoma brucei by inhibiting the enzyme serine palmitoyltransferase (SPT2) by using RNA interference or treatment with a potent SPT2 inhibitor myriocin. Mass spectrometry revealed that upon SPT2 inhibition, the parasites contained substantially reduced levels of inositolphosphorylceramide. Although phosphatidylcholine and cholesterol levels were increased to compensate for this loss, the cells were ultimately not viable. The most striking result of sphingolipid reduction in procyclic T. brucei was aberrant cytokinesis, characterized by incomplete cleavage-furrow formation, delayed kinetoplast segregation and emergence of cells with abnormal DNA content. Organelle replication continued despite sphingolipid depletion, indicating that sphingolipids act as second messengers regulating cellular proliferation and completion of cytokinesis. Distention of the mitochondrial membrane, formation of multilamellar structures within the mitochondrion and near the nucleus, accumulation of lipid bodies and, less commonly, disruption of the Golgi complex were observed after prolonged sphingolipid depletion. These findings suggest that some aspects of vesicular trafficking may be compromised. However, flagellar membrane targeting and the association of the flagellar membrane protein calflagin with detergent-resistant membranes were not affected, indicating that the vesicular trafficking defects were mild. Our studies indicate that sphingolipid biosynthesis is vital for cell cycle progression and cell survival, but not essential for the normal trafficking of flagellar membrane-associated proteins or lipid raft formation in procyclic T. brucei.

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Dissociation of Cytokinesis Initiation from Mitotic Control in a Eukaryote

Cited by 84 publications

References 48 publications

Two distinct cytokinesis pathways drive trypanosome cell division initiation from opposite cell ends

Two distinct cytokinesis pathways drive trypanosome cell division initiation from opposite cell ends

The flagellum of Trypanosoma brucei: New tricks from an old dog

Sphingolipid synthesis is necessary for kinetoplast segregation and cytokinesis in Trypanosoma brucei

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