Nu
            <scp>MA</scp>
            assemblies organize microtubule asters to establish spindle bipolarity in acentrosomal human cells

Chinen, Takumi; Yamamoto, Shohei; Takeda, Yutaka; Watanabe, Kageaki; Kuroki, Kanako; Hashimoto, Kaho; Takao, Daisuke; Kitagawa, Daiju

doi:10.15252/embj.2019102378

Cited by 105 publications

(51 citation statements)

References 78 publications

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“…We treated human cells with centrinone to create artificial acentrosomal cells (Chinen et al, 2020). We confirmed that these cells displayed prolonged mitotic duration and increased frequency of chromosome segregation errors, consistent with previous studies using centrinone (Meitinger et al, 2016;Wong et al, 2015).…”

Section: Chinen Et Al 2020supporting

confidence: 88%

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Centrosomal and Non-centrosomal Functions Emerged through Eliminating Centrosomes

Takeda

Kuroki

Chinen

et al. 2020

Cell Struct. Funct.

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Centrosomes are highly conserved organelles that act as the major microtubuleorganizing center (MTOC) in animal somatic cells. Through their MTOC activity, centrosomes play various roles throughout the cell cycle, such as supporting cell migration in interphase and spindle organization and positioning in mitosis. Various approaches for removing centrosomes from somatic cells have been developed and applied over the past few decades to understand the precise roles of centrosomes. Centrinone, a reversible and selective PLK4 (polo-like kinase 4) inhibitor, has recently emerged as an efficient approach to eliminate centrosomes. In this review, we describe the latest findings on centrosome function that have been revealed using various centrosome-eliminating approaches. In addition, we discuss our recent findings on the mechanism of centrosome-independent spindle bipolarization, discovered through the use of centrinone.

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Section: Chinen Et Al 2020supporting

confidence: 88%

“…Importantly, we found that NuMA promoted the initial steps of spindle bipolarization in early mitosis even in cells with centrosomes (Chinen et al, 2020). We observed that the time from NEBD to bipolarity establishment prolonged upon depletion of NuMA.…”

Section: Chinen Et Al 2020mentioning

confidence: 64%

Centrosomal and Non-centrosomal Functions Emerged through Eliminating Centrosomes

Takeda

Kuroki

Chinen

et al. 2020

Cell Struct. Funct.

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“…With PLK4 inhibition, centriole duplication is disrupted, causing spindles to assemble through acentriolar organization of PCM [15][16][17]. However, the role of PLK1 and/or PLK4 at mitotic centrosomes in the early zebrafish embryo is unknown.…”

Section: Plk1 and Plk4 Activity Are Required For Asymmetric Mitotic Cmentioning

confidence: 99%

PLK1- and PLK4-mediated asymmetric mitotic centrosome size and positioning in the early zebrafish embryo

Rathbun

Aljiboury

Bai

et al. 2020

Preprint

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Factors that regulate mitotic spindle positioning have been elucidated in vitro, however it remains unclear how a spindle is placed within the confines of extremely large cells. Our studies identified a uniquely large centrosome structure in the early zebrafish embryo (246.44±11.93μm 2 mitotic centrosome in a 126.86±0.35μm diameter cell), whereas C. elegans centrosomes are notably smaller (6.75±0.28μm 2 mitotic centrosome in a 55.83±1.04μm diameter cell). During early embryonic cell divisions, cell size changes rapidly in C. elegans and zebrafish embryos. Notably, mitotic centrosome area scales closely with changing cell size compared to changes in spindle length for both organisms. One interesting difference between the two is that mitotic centrosomes are asymmetric in size across embryonic zebrafish spindles, with the larger mitotic centrosome being 2.14±0.13-fold larger in size than the smaller. The largest mitotic centrosome is placed towards the embryo center in a Polo-Like Kinase (PLK) 1 and PLK4 dependent manner 87.14±4.16% of the time. We propose a model in which uniquely large centrosomes direct spindle placement within the disproportionately large zebrafish embryo cells to orchestrate cell divisions during early embryogenesis.

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“…This pathway is functional in vivo in several cell types which are naturally devoid of centrosomes (eg. vertebrate oocytes and plants) or animal somatic cells which are experimentally (chemically, genetically or physically) manipulated to eliminate their centrosomes [104][105][106]. Interestingly, in this acentrosomal pathway, both in vitro and in vivo, Kinesin-5 also plays a major role in the formation of antiparallel microtubule bundles and the generation of an outward force.…”

Section: Force Generation In the Acentrosomal Cellsmentioning

confidence: 99%

“…Interestingly, in this acentrosomal pathway, both in vitro and in vivo, Kinesin-5 also plays a major role in the formation of antiparallel microtubule bundles and the generation of an outward force. However, in contrast with the centrosome-dependent pathway, Kinesin-14 and Dynein appear to act collaboratively, rather than antagonistically, with Kinesin-5 [105,107]. Therefore, the importance of the force balance for bipolar spindle formation and its underlying mechanism have not been addressed explicitly in the acentrosomal cells and awaits further investigation.…”

Section: Force Generation In the Acentrosomal Cellsmentioning

confidence: 99%

How Essential Kinesin-5 Becomes Non-Essential: Force Balance and Microtubule Dynamics Matter

Yukawa¹,

Teratani²,

Toda³

2020

Preprint

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The bipolar mitotic spindle drives accurate chromosome segregation by capturing the kinetochore and pulling each set of sister chromatids to the opposite poles. In this review, we describe recent findings on the multiple pathways leading to bipolar spindle formation in fission yeast and discuss these results from a broader perspective. Roles of four mitotic kinesins (Kinesin-5, Kinesin-6, Kinesin-12 and Kinesin-14) in spindle assembly are depicted, and how a group of microtubule-associated proteins, sister chromatid cohesion and the kinetochore collaborates with these motors is shown. We have paid special attention to the molecular pathways that render otherwise essential Kinesin-5 to become non-essential: how cells build bipolar mitotic spindles without the need for Kinesin-5 and where the alternate forces come from are considered. We highlight the force balance for bipolar spindle assembly and explain how outward and inward forces are generated by various ways, in which the proper fine-tuning of microtubule dynamics plays a crucial role. Overall, these new pathways have illuminated remarkable plasticity and adaptability of spindle mechanics. Kinesin molecules are regarded as prospective targets for cancer chemotherapy and many specific inhibitors have been developed. However, several hurdles have arisen against their clinical implementation. This review provides insight into possible strategies to overcome these challenges.

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Nu MA assemblies organize microtubule asters to establish spindle bipolarity in acentrosomal human cells

Cited by 105 publications

References 78 publications

Centrosomal and Non-centrosomal Functions Emerged through Eliminating Centrosomes

Centrosomal and Non-centrosomal Functions Emerged through Eliminating Centrosomes

PLK1- and PLK4-mediated asymmetric mitotic centrosome size and positioning in the early zebrafish embryo

How Essential Kinesin-5 Becomes Non-Essential: Force Balance and Microtubule Dynamics Matter

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