CLIP‐170 tethers kinetochores to microtubule plus ends against poleward force by dynein for stable kinetochore–microtubule attachment

Amin, Mohammed A.; Kobayashi, Kinue; Tanaka, Kozo

doi:10.1016/j.febslet.2015.07.036

Cited by 8 publications

(6 citation statements)

References 29 publications

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“…It is of note that Zw10 is not only responsible for kinetochore localization of dynein, but also that of CLIP-170 through dynactin 49 . Our recent data suggest that CLIP-170 plays a role in tethering kinetochores to microtubule ends to resist the dynein-mediated poleward force, which is independent of CENP-E 50 , implicating CLIP-170 in lateral attachment.…”

Section: Discussionmentioning

confidence: 89%

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: Discussionmentioning

confidence: 89%

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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“…Moreover, phosphorylation of CLIP-170 at S312 by Plk1 regulates its binding to microtubules and is crucial for chromosome alignment [105]. CLIP-170 appears to promote kinetochore-microtubule attachments and chromosome congression by counteracting Dynein/Dynactin [106]. The XMAP215/Ch-TOG and CLASP families of +TIPs have also been implicated in chromosome congression.…”

Section: Mechanisms Of Chromosome Congressionmentioning

confidence: 99%

Mechanisms of Chromosome Congression during Mitosis

Maiato

Gomes

Sousa

et al. 2017

Biology

170

176

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Chromosome congression during prometaphase culminates with the establishment of a metaphase plate, a hallmark of mitosis in metazoans. Classical views resulting from more than 100 years of research on this topic have attempted to explain chromosome congression based on the balance between opposing pulling and/or pushing forces that reach an equilibrium near the spindle equator. However, in mammalian cells, chromosome bi-orientation and force balance at kinetochores are not required for chromosome congression, whereas the mechanisms of chromosome congression are not necessarily involved in the maintenance of chromosome alignment after congression. Thus, chromosome congression and maintenance of alignment are determined by different principles. Moreover, it is now clear that not all chromosomes use the same mechanism for congressing to the spindle equator. Those chromosomes that are favorably positioned between both poles when the nuclear envelope breaks down use the so-called “direct congression” pathway in which chromosomes align after bi-orientation and the establishment of end-on kinetochore-microtubule attachments. This favors the balanced action of kinetochore pulling forces and polar ejection forces along chromosome arms that drive chromosome oscillatory movements during and after congression. The other pathway, which we call “peripheral congression”, is independent of end-on kinetochore microtubule-attachments and relies on the dominant and coordinated action of the kinetochore motors Dynein and Centromere Protein E (CENP-E) that mediate the lateral transport of peripheral chromosomes along microtubules, first towards the poles and subsequently towards the equator. How the opposite polarities of kinetochore motors are regulated in space and time to drive congression of peripheral chromosomes only now starts to be understood. This appears to be regulated by position-dependent phosphorylation of both Dynein and CENP-E and by spindle microtubule diversity by means of tubulin post-translational modifications. This so-called “tubulin code” might work as a navigation system that selectively guides kinetochore motors with opposite polarities along specific spindle microtubule populations, ultimately leading to the congression of peripheral chromosomes. We propose an integrated model of chromosome congression in mammalian cells that depends essentially on the following parameters: (1) chromosome position relative to the spindle poles after nuclear envelope breakdown; (2) establishment of stable end-on kinetochore-microtubule attachments and bi-orientation; (3) coordination between kinetochore- and arm-associated motors; and (4) spatial signatures associated with post-translational modifications of specific spindle microtubule populations. The physiological consequences of abnormal chromosome congression, as well as the therapeutic potential of inhibiting chromosome congression are also discussed.

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“…S2 A ). Next, we disrupted their function by treating with specific siRNAs and employing published protocols ( 44 , 45 , 46 ). We confirmed the efficiency of depletion of the target proteins by immunoblotting ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Coordination between the Ndc80 complex and dynein is essential for microtubule plus-end capture by kinetochores during early mitosis

Amin¹,

Chakraborty²,

Wallace³

et al. 2023

Journal of Biological Chemistry

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CLIP‐170 tethers kinetochores to microtubule plus ends against poleward force by dynein for stable kinetochore–microtubule attachment

Cited by 8 publications

References 29 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

Mechanisms of Chromosome Congression during Mitosis

Coordination between the Ndc80 complex and dynein is essential for microtubule plus-end capture by kinetochores during early mitosis

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