Morphology of the Trypanosome Bilobe, a Novel Cytoskeletal Structure

Esson, Heather J.; Morriswood, Brooke; Yavuz, Sevil; Vidilaseris, Keni; Dong, Gang; Warren, Graham

doi:10.1128/ec.00219-12

Cited by 12 publications

(27 citation statements)

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“…The furrow frequently stalled at a position in the cell body between the two nuclei, near where the new tapered posterior end would begin to form. This location is similar to the very posterior end of the old FAZ, where the MtQ passes between the centrin arm and hook complex, then wraps around the FP (Esson et al ., ). It is possible that either the track the cleavage furrow follows or the specific mode of furrow ingression changes at this point to require the force producing properties of KLIF.…”

Section: Discussionmentioning

confidence: 97%

“…The flagellum is nucleated by a basal body that docks to the base of the flagellar pocket (FP), which is an invagination of the plasma membrane that functions as the sole site of endo‐ and exo‐cytosis (Field and Carrington, ; Lacomble et al ., ). The top of the FP is tightly apposed to the flagellar membrane by a series of cytoskeletal structures, including the flagella pocket collar, the hook complex and the centrin arm (Esson et al ., ; Morriswood, ; Perdomo et al ., ). Once the flagellum emerges onto the cell surface, it is attached to the cell body by the flagellum attachment zone (FAZ), which forms a series of desmosome‐like structures that span the plasma and flagellar membranes to form a tight seal (Sunter and Gull, ; Vickerman, ).…”

Section: Introductionmentioning

confidence: 99%

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Identification of TOEFAZ1‐interacting proteins reveals key regulators of Trypanosoma brucei cytokinesis

Hilton

Sladewski

Perry

et al. 2018

Molecular Microbiology

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The protist parasite Trypanosoma brucei is an obligate extracellular pathogen that retains its highly polarized morphology during cell division and has evolved a novel cytokinetic process independent of non-muscle myosin II. The polo-like kinase homolog TbPLK is essential for transmission of cell polarity during division and for cytokinesis. We previously identified a putative TbPLK substrate named Tip of the Extending FAZ 1 (TOEFAZ1) as an essential kinetoplastid-specific component of the T. brucei cytokinetic machinery. We performed a proximity-dependent biotinylation identification (BioID) screen using TOEFAZ1 as a means to identify additional proteins that are involved in cytokinesis. Using quantitative proteomic methods, we identified nearly 500 TOEFAZ1-proximal proteins and characterized 59 in further detail. Among the candidates, we identified an essential putative phosphatase that regulates the expression level and localization of both TOEFAZ1 and TbPLK, a previously uncharacterized protein that is necessary for the assembly of a new cell posterior, and a microtubule plus-end directed orphan kinesin that is required for completing cleavage furrow ingression. The identification of these proteins provides new insight into T. brucei cytokinesis and establishes TOEFAZ1 as a key component of this essential and uniquely configured process in kinetoplastids.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Identification of TOEFAZ1‐interacting proteins reveals key regulators of Trypanosoma brucei cytokinesis

Hilton

Sladewski

Perry

et al. 2018

Molecular Microbiology

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“…2) indicated that the drug blocked the entry of trypanosomes into the S-phase. The bilobe, a centrincontaining cytoskeletal structure at the base of the flagellum (Esson et al, 2012), is duplicated in S-phase (Zhou et al, 2014). We postulated that because AEE788 prevented S-phase entry (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Cytokinesis requires duplication of the flagellum and its associated cytoskeletal structures (Robinson et al, 1995;Kohl et al, 2003). The bilobe is a cytoskeletal structure closely associated with the FAZ filament (Esson et al, 2012) and is implicated in FAZ formation (Zhou et al, 2010;Bangs, 2011). The flagellar pocket is the major site of endocytosis, a process needed for nutrient uptake (for review, Field et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

AEE788 Inhibits Basal Body Assembly and Blocks DNA Replication in the African Trypanosome

et al. 2017

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causes human African trypanosomiasis (HAT). The pyrrolopyrimidine AEE788 (a hit for anti-HAT drug discovery) associates with three trypanosome protein kinases. Herein we delineate the effects of AEE788 on using chemical biology strategies. AEE788 treatment inhibits DNA replication in the kinetoplast (mitochondrial nucleoid) and nucleus. In addition, AEE788 blocks duplication of the basal body and the bilobe without affecting mitosis. Thus, AEE788 prevents entry into the S-phase of the cell division cycle. To study the kinetics of early events in trypanosome division, we employed an "AEE788 block and release" protocol to stage entry into the S-phase. A time-course of DNA synthesis (nuclear and kinetoplast DNA), duplication of organelles (basal body, bilobe, kinetoplast, nucleus), and cytokinesis was obtained. Unexpected findings include the following: 1) basal body and bilobe duplication are concurrent; 2) maturation of probasal bodies, marked by TbRP2 recruitment, is coupled with nascent basal body assembly, monitored by localization of TbSAS6 at newly forming basal bodies; and 3) kinetoplast division is observed in G2 after completion of nuclear DNA synthesis. Prolonged exposure of trypanosomes to AEE788 inhibited transferrin endocytosis, altered cell morphology, and decreased cell viability. To discover putative effectors for the pleiotropic effects of AEE788, proteome-wide changes in protein phosphorylation induced by the drug were determined. Putative effectors include an SR protein kinase, bilobe proteins, TbSAS4, TbRP2, and BILBO-1. Loss of function of one or more of these effectors can, from published literature, explain the polypharmacology of AEE788 on trypanosome biology.

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“…Above the flagellar pocket collar are at least two other cytoskeletal complexes – the hook complex, which contains the repeat motif protein TbMORN1, and the centrin arm, which contains at least two of the five trypanosome centrin isoforms (Esson et al . 2012).…”

Section: The Life Cycle and Morphology Of T Bruceimentioning

confidence: 99%

Let's get fISSical: fastin silicosynchronization as a new tool for cell division cycle analysis

Morriswood

Engstler

2017

Parasitology

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SUMMARYCell cycle progression is a question of fundamental biological interest. The coordinated duplication and segregation of all cellular structures and organelles is however an extremely complex process, and one which remains only partially understood even in the most intensively researched model organisms. Trypanosomes are in an unusual position in this respect – they are both outstanding model systems for fundamental questions in eukaryotic cell biology, and pathogens that are the causative agents of three of the neglected tropical diseases. As a failure to successfully complete cell division will be deleterious or lethal, analysis of the cell division cycle is of relevance both to basic biology and drug design efforts. Cell division cycle analysis is however experimentally challenging, as the analysis of phenotypes associated with it remains hypothesis-driven and therefore biased. Current methods of analysis are extremely labour-intensive, and cell synchronization remains difficult and unreliable. Consequently, there exists a need – both in basic and applied trypanosome biology – for a global, unbiased, standardized and high-throughput analysis of cell division cycle progression. In this review, the requirements – both practical and computational – for such a system are considered and compared with existing techniques for cell cycle analysis.

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Morphology of the Trypanosome Bilobe, a Novel Cytoskeletal Structure

Cited by 12 publications

References 0 publications

Identification of TOEFAZ1‐interacting proteins reveals key regulators of Trypanosoma brucei cytokinesis

Identification of TOEFAZ1‐interacting proteins reveals key regulators of Trypanosoma brucei cytokinesis

AEE788 Inhibits Basal Body Assembly and Blocks DNA Replication in the African Trypanosome

Let's get fISSical: fastin silicosynchronization as a new tool for cell division cycle analysis

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