Heterogeneous architecture of vertebrate kinetochores revealed by three-dimensional superresolution fluorescence microscopy

Wynne, David J.

doi:10.1091/mbc.e16-02-0130

Cited by 20 publications

(18 citation statements)

References 47 publications

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“…As shown in Fig. 4A and B , kinetochore localization of BubR1, a SAC component, decreased as reported previously 27 – 29 . Kinetochore localization of DIC, Zw10, and Spindly also markedly decreased when Aurora B activity was inhibited.…”

Section: Resultssupporting

confidence: 88%

“…Considering that kinetochores form lateral microtubule attachments in the prometaphase rosette, molecules involved in lateral attachment are supposedly included among them. These molecules overlap with components of the expandable module on unattached kinetochores reported by Wynne and Funabiki 28 , 29 . Among these, the RZZ complex was recently suggested to form higher-order oligomers that may be a molecular basis for the fibrous corona, a kinetochore structure visible only before microtubule attachment 48 .…”

Section: Discussionsupporting

confidence: 54%

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Lateral attachment of kinetochores to microtubules is enriched in prometaphase rosette and facilitates chromosome alignment and bi-orientation establishment

Itoh

Ikeda

Iemura

et al. 2018

Sci Rep

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Faithful chromosome segregation is ensured by the establishment of bi-orientation; the attachment of sister kinetochores to the end of microtubules extending from opposite spindle poles. In addition, kinetochores can also attach to lateral surfaces of microtubules; called lateral attachment, which plays a role in chromosome capture and transport. However, molecular basis and biological significance of lateral attachment are not fully understood. We have addressed these questions by focusing on the prometaphase rosette, a typical chromosome configuration in early prometaphase. We found that kinetochores form uniform lateral attachments in the prometaphase rosette. Many transient kinetochore components are maximally enriched, in an Aurora B activity-dependent manner, when the prometaphase rosette is formed. We revealed that rosette formation is driven by rapid poleward motion of dynein, but can occur even in its absence, through slow kinetochore movements caused by microtubule depolymerization that is supposedly dependent on kinetochore tethering at microtubule ends by CENP-E. We also found that chromosome connection to microtubules is extensively lost when lateral attachment is perturbed in cells defective in end-on attachment. Our findings demonstrate that lateral attachment is an important intermediate in bi-orientation establishment and chromosome alignment, playing a crucial role in incorporating chromosomes into the nascent spindle.

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Section: Resultssupporting

confidence: 88%

Section: Discussionsupporting

confidence: 54%

Lateral attachment of kinetochores to microtubules is enriched in prometaphase rosette and facilitates chromosome alignment and bi-orientation establishment

Itoh

Ikeda

Iemura

et al. 2018

Sci Rep

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“…Upon drug washout, spindles reform in a manner that promotes merotelic attachment ( Kapoor et al., 2000 ). Compared with nocodazole treatment, monastrol-treated cells displayed significantly lower kinetochore expansion as measured by CENP-E-marked outer kinetochore size ( Figures 3 A and 3B), in agreement with previous studies demonstrating that the majority of kinetochores remain attached syntelically to MTs upon Eg5 inhibition ( Kapoor et al., 2000 ) and that expansion is not observed in Xenopus ( Wynne and Funabiki, 2016 ) or human cells under these conditions ( Sacristan et al., 2018 ). Monastrol washout treatment induced similar total lagging chromosome rates and also significantly enriched lagging of chromosomes 1 and 2 ( Figures 3 C–3E), suggesting that this bias is independent of extensive kinetochore expansion associated with nocodazole treatment.…”

Section: Resultssupporting

confidence: 90%

Non-random Mis-segregation of Human Chromosomes

Worrall¹,

Tamura²,

Mazzagatti³

et al. 2018

Cell Reports

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SummaryA common assumption is that human chromosomes carry equal chances of mis-segregation during compromised cell division. Human chromosomes vary in multiple parameters that might generate bias, but technological limitations have precluded a comprehensive analysis of chromosome-specific aneuploidy. Here, by imaging specific centromeres coupled with high-throughput single-cell analysis as well as single-cell sequencing, we show that aneuploidy occurs non-randomly following common treatments to elevate chromosome mis-segregation. Temporary spindle disruption leads to elevated mis-segregation and aneuploidy of a subset of chromosomes, particularly affecting chromosomes 1 and 2. Unexpectedly, we find that a period of mitotic delay weakens centromeric cohesion and promotes chromosome mis-segregation and that chromosomes 1 and 2 are particularly prone to suffer cohesion fatigue. Our findings demonstrate that inherent properties of individual chromosomes can bias chromosome mis-segregation and aneuploidy rates, with implications for studies on aneuploidy in human disease.

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“…The past decade not only witnessed the emerging application of super-resolution microscopy in centrosome research but also in the study of many other subcellular organelles and structures, including chromatin, which is mostly resolved by SMLM (Bintu et al 2018;Birk 2019;Sieben et al 2018b;Wang et al 2016;Xu and Liu 2019), the centromere and kinetochore (Joglekar et al 2009;Wan et al 2009;Wynne and Funabiki 2016), the contractile ring (Laplante et al 2016;McDonald et al 2017), the nuclear pore complex (Hurt and Beck 2015;Loschberger et al 2012;Szymborska et al 2013), and the mitochondria (Brown et al 2010;Jakobs and Wurm 2014;Jans et al 2013).…”

Section: Applications Beyond Centrosomementioning

confidence: 99%

Super-resolution microscopy: successful applications in centrosome study and beyond

Zhang

2019

Biophys Rep

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Centrosome is the main microtubule-organizing center in most animal cells. Its core structure, centriole, also assembles cilia and flagella that have important sensing and motility functions. Centrosome has long been recognized as a highly conserved organelle in eukaryotic species. Through electron microscopy, its ultrastructure was revealed to contain a beautiful nine-symmetrical core 60 years ago, yet its molecular basis has only been unraveled in the past two decades. The emergence of super-resolution microscopy allows us to explore the insides of a centrosome, which is smaller than the diffraction limit of light. Super-resolution microscopy also enables the compartmentation of centrosome proteins into different zones and the identification of their molecular interactions and functions. This paper compiles the centrosome architecture knowledge that has been revealed in recent years and highlights the power of several super-resolution techniques.

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Heterogeneous architecture of vertebrate kinetochores revealed by three-dimensional superresolution fluorescence microscopy

Cited by 20 publications

References 47 publications

Lateral attachment of kinetochores to microtubules is enriched in prometaphase rosette and facilitates chromosome alignment and bi-orientation establishment

Lateral attachment of kinetochores to microtubules is enriched in prometaphase rosette and facilitates chromosome alignment and bi-orientation establishment

Non-random Mis-segregation of Human Chromosomes

Super-resolution microscopy: successful applications in centrosome study and beyond

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