The Flagellum Attachment Zone: ‘The Cellular Ruler’ of Trypanosome Morphology

Sunter, Jack D.; Gull, Keith

doi:10.1016/j.pt.2015.12.010

Cited by 96 publications

(147 citation statements)

References 61 publications

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“…In the old flagellum, tubulin does not need to be replaced and therefore the loss of IFT does not result in flagellum shortening. This absence of shortening could be due to the sophisticated architecture of the trypanosome flagellum that contains a PFR physically connected to the axoneme and that is attached along most of the length of the cell body via another cytoskeletal structure called the flagellum attachment zone (Sunter and Gull, 2016). Accordingly, when trypanosomes produce developmental stages with a shorter flagellum length, this is always achieved by mean of an asymmetric division with the construction of a shorter new flagellum and not by shortening an existing flagellum (Ooi and Bastin, 2013;Rotureau et al, 2011;Sharma et al, 2008).…”

Section: Discussion Ift Is Not Required For the Maintenance Of Flagelmentioning

confidence: 99%

Intraflagellar transport is required for the maintenance of the trypanosome flagellum composition but not its length

Fort

Bonnefoy

Kohl

et al. 2016

Journal of Cell Science

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Intraflagellar transport (IFT) is required for construction of most cilia and flagella. Here, we used electron microscopy, immunofluorescence and live video microscopy to show that IFT is absent or arrested in the mature flagellum of Trypanosoma brucei upon RNA interference (RNAi)-mediated knockdown of IFT88 and IFT140, respectively. Flagella assembled prior to RNAi did not shorten, showing that IFT is not essential for the maintenance of flagella length. Although the ultrastructure of the axoneme was not visibly affected, flagellar beating was strongly reduced and the distribution of several flagellar components was drastically modified. The R subunit of the protein kinase A was no longer concentrated in the flagellum but was largely found in the cell body whereas the kinesin 9B motor was accumulating at the distal tip of the flagellum. In contrast, the distal tip protein FLAM8 was dispersed along the flagellum. This reveals that IFT also functions in maintaining the distribution of some flagellar proteins after construction of the organelle is completed.

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Section: Discussion Ift Is Not Required For the Maintenance Of Flagelmentioning

confidence: 99%

Intraflagellar transport is required for the maintenance of the trypanosome flagellum composition but not its length

Fort

Bonnefoy

Kohl

et al. 2016

Journal of Cell Science

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“…1F). However, given that the FAZ structure contains several domains (25), the precise location of CIF2 at the new FAZ tip remains to be determined.…”

Section: Identification Of Cif1-binding Proteins and Near Neighborsmentioning

confidence: 99%

An EF-hand-containing Protein in Trypanosoma brucei Regulates Cytokinesis Initiation by Maintaining the Stability of the Cytokinesis Initiation Factor CIF1

Zhou¹,

Hu²,

Li³

2016

Journal of Biological Chemistry

110

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Trypanosoma brucei undergoes cytokinesis uni-directionally from the anterior tip of the new flagellum attachment zone (FAZ) toward the posterior end of the cell. We recently delineated a novel signaling pathway composed of polo-like kinase, cytokinesis initiation factor 1 (CIF1), and aurora B kinase that acts in concert at the new FAZ tip to regulate cytokinesis initiation. To identify new cytokinesis regulators, we carried out proximity-dependent biotin identification and identified many CIF1 binding partners and near neighbors. Here we report a novel CIF1-binding protein, named CIF2, and its mechanistic role in cytokinesis initiation. CIF2 interacts with CIF1 in vivo and co-localizes with CIF1 at the new FAZ tip during early cell cycle stages. RNAi of CIF2 inhibited the normal, anterior-toposterior cytokinesis but activated an alternative, posterior-toanterior cytokinesis. CIF2 depletion destabilized CIF1 and disrupted the localization of polo-like kinase and aurora B kinase to the new FAZ tip, thus revealing the mechanistic role of CIF2 in cytokinesis initiation. Surprisingly, overexpression of CIF2 also inhibited the normal, anterior-to-posterior cytokinesis and triggered the alternative, posterior-to-anterior cytokinesis, suggesting a tight control of CIF2 protein abundance. These results identified a new regulator in the cytokinesis regulatory pathway and reiterated that a backup cytokinesis pathway is activated by inhibiting the normal cytokinesis pathway.Trypanosoma brucei, an early divergent parasitic protozoan causing sleeping sickness in humans and nagana in cattle in sub-Saharan Africa, possesses a complex life cycle by alternating between the insect vector and the mammalian host. Within the insect midgut and the mammalian bloodstream, the parasite proliferates through binary fission along its longitudinal axis between the two flagella and their associated cytoskeletal structure termed flagellum attachment zone (FAZ) 2 (1). The cell division plane in a dividing trypanosome is determined by the length of the elongating new flagellum/FAZ, and the anterior tip of the new FAZ constitutes the site from which cytokinesis cleavage furrow ingression is initiated (2, 3). Before cytokinesis cleavage furrow initiation, invagination of cell body occurs between the two flagella, leading to the formation of the so-called division fold (4). Subsequently, the anterior tip of the new flagellum is released from the old flagellum due to the dissolution of the flagella connector (5), and cleavage furrow ingression begins from the anterior tip of the new FAZ and proceeds along the division fold toward the posterior end of the cell (6). At the very late stage of cytokinesis, the two daughter cells are connected at the posterior ends via a thread of membrane termed the cytoplasmic bridge (4), which is finally severed to generate two uni-flagellate daughter cells. Although the morphological events of cytokinesis in T. brucei have been well described (4), the mechanisms underlying this unusual mode of cytokinesis and the reg...

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“…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, 2012;Morriswood, 2015;Perdomo et al, 2016). 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, 2016;Vickerman, 1969). A set of four microtubules known as the microtubule quartet (MtQ) that nucleate at the basal body and are thought to have opposing polarity to the subpellicular microtubules are found next to the FAZ filament (Lacomble et al, 2009(Lacomble et al, , 2012.…”

Section: Introductionmentioning

confidence: 99%

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

Hilton

Sladewski

Perry

et al. 2018

Molecular Microbiology

104

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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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The Flagellum Attachment Zone: ‘The Cellular Ruler’ of Trypanosome Morphology

Cited by 96 publications

References 61 publications

Intraflagellar transport is required for the maintenance of the trypanosome flagellum composition but not its length

Intraflagellar transport is required for the maintenance of the trypanosome flagellum composition but not its length

An EF-hand-containing Protein in Trypanosoma brucei Regulates Cytokinesis Initiation by Maintaining the Stability of the Cytokinesis Initiation Factor CIF1

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

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