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

Zhou, Qing; Gu, Jianhua; Zhao, Lun; Ayala, Francisco J.; Li, Ziyin

doi:10.1073/pnas.1601596113

Cited by 52 publications

(183 citation statements)

References 36 publications

(50 reference statements)

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“…We recently delineated a novel cytokinesis signaling pathway, composed of TbPLK, TbAUK1, and a trypanosome-specific protein CIF1, that acts in concert at the new FAZ tip to promote cytokinesis initiation (11). TbPLK phosphorylates CIF1 during early cell cycle stages, and this phosphorylation is required for CIF1 localization to the new FAZ tip.…”

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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

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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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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

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110

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“…In vivo studies show CIF2 interacting with CIF1. Furthermore, both of them colocalize at the new FAZ tip during early cell cycle stages [58,59]. By inhibiting typical anterior-toposterior cytokinesis, these studies characterized a backup cytokinesis pathway located at the posterior end of the cell [59] (Figure 5D-I).…”

Section: Paraflagellar Structure and Flagellum Attachment Zonementioning

confidence: 91%

“…Despite a normal growth rate, this phenotype highlights FAZ as an important structure in orchestrating basal body positions and determining the plane of cytokinesis. Recently, during T. brucei cytokinesis, a novel signaling pathway was described; it is composed of Polo-like kinase, CIF1, CIF2 and Aurora B kinase [58]. These signaling molecules behave as cytokinesis initiation regulators.…”

Section: Paraflagellar Structure and Flagellum Attachment Zonementioning

confidence: 99%

Morphological and Functional Aspects of Cytoskeleton of Trypanosomatids

Vidal¹,

Souza²

2017

Cytoskeleton - Structure, Dynamics, Function and Disease

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Trypanosomatidae are protozoans that include monogenetic parasites, such as the Blastocrithidia and Herpetomonas genera, as well as digenetic parasites, such as the Tr yp an os oma and Leishmania genera. Their life cycles alternate between insect vectors and mammalian hosts. The parasite's life cycle involves symmetrical division and different transitional developmental stages. In trypanosomatids, the cytoskeleton is composed of subpellicular microtubules organized in a highly ordered array of stable microtubules located beneath the plasma membrane, the paraflagellar rod, which is a lattice-like structure attached alongside the flagellar axoneme and a cytostome-cytopharynx. The complex life cycle, the extremely precise cytoskeletal organization and the single copy structures present in trypanosomatids provide interesting models for cell biology studies. The introduction of molecular biology, FIB/SEM (focused ion beam scanning electron microscopy) and electron microscopy tomography approaches and classical methods, such as negative staining, chemical fixation and ultrafast cryofixation have led to the determination of the three-dimensional (3D) structural organization of the cells. In this chapter, we highlight the recent findings on Trypanosomatidae cytoskeleton emphasizing their structural organization and the functional role of proteins involved in the biogenesis and duplication of cytoskeletal structures. The principal finding of this review is that all approaches listed above enhance our knowledge of trypanosomatids biology showing that cytoskeleton elements are essential to several important events throughout the protozoan life cycle.

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“…These results delineate a novel signaling cascade from Polo-like kinase through CIF1 to Aurora B kinase, and demonstrate a concerted action of the 3 proteins at the new FAZ tip for cytokinesis initiation. 4 This cytokinesis signaling pathway is totally different from that in fungi and animals. Given that trypanosomes diverged from the last eukaryotic common ancestor before fungi and animals, it is likely that the trypanosome cytokinesis regulatory pathway may reflect certain features of the ancestral cytokinesis pathway.…”

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confidence: 99%

“…3,4 Subsequently, furrow ingression is initiated from the anterior tip of the new FAZ filament, and proceeds, along the division fold, to the posterior. Therefore, the new FAZ tip constitutes the cytokinesis initiation site in trypanosomes.…”

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confidence: 99%