Kinesin-14 Family Proteins HSET/XCTK2 Control Spindle Length by Cross-Linking and Sliding Microtubules

Cai, Shanbao; Weaver, Lesley N.; Ems-McClung, Stephanie C.; Walczak, Claire

doi:10.1091/mbc.e08-09-0971

Cited by 176 publications

(224 citation statements)

References 68 publications

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“…Compared with CENP-E, Kid is a fast, but low processive motor 26 , which is probably why it works irrespective of microtubule stability. In a previous study, it was reported that chromosome alignment in cells depleted of Nuf2, a component of the Ndc80 complex, was significantly restored by co-depletion of HSET 2 , a minus-end-directed motor belonging to the kinesin-14 family 27,28 . We confirmed that the kinetochore to spindle equator distance was decreased by co-depletion of HSET in Hec1-depleted cells (Fig.…”

Section: Article Nature Communicationsmentioning

confidence: 97%

Chromokinesin Kid and kinetochore kinesin CENP-E differentially support chromosome congression without end-on attachment to microtubules

Iemura

Tanaka

2015

Nat Commun

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Chromosome congression is the alignment of chromosomes at the spindle equator, and is a prerequisite for faithful chromosome segregation. Recent data suggest that before kinetochores attach to the end of microtubules (end-on attachment), chromosomes can move along microtubules towards the spindle equator through attachment of kinetochores to the lateral surface of microtubules (lateral attachment). Here we address this mechanism, focusing on the contribution of two mitotic motors, Kid and CENP-E. In cells depleted of Hec1, which is essential for end-on attachment, chromosomes show partial and transient congression. This transient congression is further perturbed by co-depletion of Kid, suggesting its role in chromosome congression. In comparison, CENP-E suppresses chromosome congression, probably by tethering kinetochores to short, unstable microtubules, and works in congression only when microtubules are stabilized. Our results may reflect the differential contributions of Kid and CENP-E in chromosome congression in physiological conditions where stabilized microtubules are becoming increased.

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Section: Article Nature Communicationsmentioning

confidence: 97%

Chromokinesin Kid and kinetochore kinesin CENP-E differentially support chromosome congression without end-on attachment to microtubules

Iemura

Tanaka

2015

Nat Commun

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“…Human HSET localizes between microtubules within the mitotic spindle. 93,94 HSET inhibition has no significant impact on bipolar anaphase or cell viability in human BJ fibroblasts, which exhibit virtually no centrosome amplification (B1%), 95 as well as mouse NIH-3T3 fibroblast and human MCF-7 breast cancer cells, which exhibit only 'low-level' centrosome amplification. 6 However, in cells with a higher incidence of centrosome amplification, such as isogenic tetraploids of the aforementioned cell lines or MDA-MB-231 cells, bipolar anaphase is inhibited and viability compromised by HSET knockdown.…”

Section: Surviving With Surplus: Managing Supernumerary Centrosomes Bmentioning

confidence: 98%

“…96 Although HSET knockdown in HeLa cells does result in a minor attenuation of spindle pole focusing, central spindle stability, and microtubule density, along with a mild augmentation of spindle breadth, the occurrence of a bipolar anaphase remains unimpeded. 94 (ii) Astral microtubules are captured at kinetochores by the Ndc80 complex, thus forming kinetochore microtubules. Low-tension attachments activate the SAC, which provides time to correct the errors.…”

Section: Surviving With Surplus: Managing Supernumerary Centrosomes Bmentioning

confidence: 99%

Let's huddle to prevent a muddle: centrosome declustering as an attractive anticancer strategy

2012

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Nearly a century ago, cell biologists postulated that the chromosomal aberrations blighting cancer cells might be caused by a mysterious organelle-the centrosome-that had only just been discovered. For years, however, this enigmatic structure was neglected in oncologic investigations and has only recently reemerged as a key suspect in tumorigenesis. A majority of cancer cells, unlike healthy cells, possess an amplified centrosome complement, which they manage to coalesce neatly at two spindle poles during mitosis. This clustering mechanism permits the cell to form a pseudo-bipolar mitotic spindle for segregation of sister chromatids. On rare occasions this mechanism fails, resulting in declustered centrosomes and the assembly of a multipolar spindle. Spindle multipolarity consigns the cell to an almost certain fate of mitotic arrest or death. The catastrophic nature of multipolarity has attracted efforts to develop drugs that can induce declustering in cancer cells. Such chemotherapeutics would theoretically spare healthy cells, whose normal centrosome complement should preclude multipolar spindle formation. In search of the 'Holy Grail' of nontoxic, cancer cell-selective, and superiorly efficacious chemotherapy, research is underway to elucidate the underpinnings of centrosome clustering mechanisms. Here, we detail the progress made towards that end, highlighting seminal work and suggesting directions for future research, aimed at demystifying this riddling cellular tactic and exploiting it for chemotherapeutic purposes. We also propose a model to highlight the integral role of microtubule dynamicity and the delicate balance of forces on which cancer cells rely for effective centrosome clustering. Finally, we provide insights regarding how perturbation of this balance may pave an inroad for inducing lethal centrosome dispersal and death selectively in cancer cells.

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“…8d the hyperboloid model function with all three parameters isolated, where again the data points combine to collapse to the model surface. The reasons behind the exceptional behavior in Tobacco BY-2 cells and mouse oocytes (MI) are unknown, but we speculate that it might be related with the fact that plants in general are more tolerant to aneuploidy (Matzke et al 2003), while propagation of aneuploidy in the germline is (Goshima et al 2005), and 1.5 (Reis et al 2009) 1.2 Human HeLa 13 16 0.9 SL-14.3 (Cai et al 2009), 12.5 c (Tokai-Nishizumi et al 2005 and 12 (Jorge Ferreira, personal communication); MD-9 d (Meraldi et al 2004), 23.5 (Zhao et al 2008, 17 (Arnaoutov et al 2005), 15.2 (Kallio et al 1998) and14 (Jorge Ferreira, personal communication);and F-0.9 (Amaro et al 2010) 2.2…”

Section: A Relation Between Flux Velocity Spindle Size and Metaphasementioning

confidence: 99%

Maturation of the kinetochore-microtubule interface and the meaning of metaphase

Pereira

Maiato

2012

Chromosome Res

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Chromosome positioning at the equator of the mitotic spindle emerges out of a relatively entropic background. At this moment, termed metaphase, all kinetochores have typically captured microtubules leading to satisfaction of the spindle-assembly checkpoint, but the cell does not enter anaphase immediately. The waiting time in metaphase is related to the kinetics of securin and cyclin B1 degradation, which trigger sisterchromatid separation and promote anaphase processivity, respectively. Yet, as judged by metaphase duration, such kinetics vary widely between cell types and organisms, with no evident correlation to ploidy or cell size. During metaphase, many animal and plant spindles are also characterized by a conspicuous "flux" activity characterized by continuous poleward translocation of spindle microtubules, which maintain steady-state length and position. Whether spindle microtubule flux plays a specific role during metaphase remains arguable. Based on known experimental parameters, we have performed a comparative analysis amongst different cell types from different organisms and show that spindle length, metaphase duration and flux velocity combine within each system to obey a quasi-universal rule. As so, knowledge of two of these parameters is enough to estimate the third. This trend indicates that metaphase duration is tuned to allow approximately one kinetochore-to-pole round of microtubule flux. We propose that the time cells spend in metaphase evolved as a quality enhancement step that allows for the uniform stabilization/correction of kinetochore-microtubule attachments, thereby promoting mitotic fidelity.

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Kinesin-14 Family Proteins HSET/XCTK2 Control Spindle Length by Cross-Linking and Sliding Microtubules

Cited by 176 publications

References 68 publications

Chromokinesin Kid and kinetochore kinesin CENP-E differentially support chromosome congression without end-on attachment to microtubules

Chromokinesin Kid and kinetochore kinesin CENP-E differentially support chromosome congression without end-on attachment to microtubules

Let's huddle to prevent a muddle: centrosome declustering as an attractive anticancer strategy

Maturation of the kinetochore-microtubule interface and the meaning of metaphase

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