Regulatory mechanisms that control mitotic kinesins

Yount, Amber L; Zong, Hailing; Walczak, Claire

doi:10.1016/j.yexcr.2014.12.015

Cited by 42 publications

(41 citation statements)

References 60 publications

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“…; Yount et al. ). However, it has long been known that MTs also participate in more large‐scale morphogenetic events that shape the developing embryo.…”

Section: Introductionmentioning

confidence: 99%

“…The microtubule (MT) cytoskeleton plays a key role in many aspects of cellular function, including mitosis, centrosome dynamics and cargo transport within cells (Hancock, 2014;Venghateri et al 2015;Yount et al 2015). However, it has long been known that MTs also participate in more largescale morphogenetic events that shape the developing embryo.…”

Section: Introductionmentioning

confidence: 99%

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Microtubules, polarity and vertebrate neural tube morphogenesis

et al. 2016

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Microtubules (MTs) are key cellular components, long known to participate in morphogenetic events that shape the developing embryo. However, the links between the cellular functions of MTs, their effects on cell shape and polarity, and their role in large-scale morphogenesis remain poorly understood. Here, these relationships were examined with respect to two strategies for generating the vertebrate neural tube: bending and closure of the mammalian neural plate; and cavitation of the teleost neural rod. The latter process has been compared with 'secondary' neurulation that generates the caudal spinal cord in mammals. MTs align along the apico-basal axis of the mammalian neuroepithelium early in neural tube closure, participating functionally in interkinetic nuclear migration, which indirectly impacts on cell shape. Whether MTs play other functional roles in mammalian neurulation remains unclear. In the zebrafish, MTs are important for defining the neural rod midline prior to its cavitation, both by localizing apical proteins at the tissue midline and by orienting cell division through a mirrorsymmetric MT apparatus that helps to further define the medial localization of apical polarity proteins. Par proteins have been implicated in centrosome positioning in neuroepithelia as well as in the control of polarized morphogenetic movements in the neural rod. Understanding of MT functions during early nervous system development has so far been limited, partly by techniques that fail to distinguish 'cause' from 'effect'. Future developments will likely rely on novel ways to selectively impair MT function in order to investigate the roles they play.

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“…; Yount et al. ). However, it has long been known that MTs also participate in more large‐scale morphogenetic events that shape the developing embryo.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Microtubules, polarity and vertebrate neural tube morphogenesis

et al. 2016

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“…One class of proteins that plays a major role in spindle formation and function are mitotic motor proteins that generate forces for centrosome separation, microtubule sliding and clustering, microtubule dynamics, and chromosome motion (Yount, Zong, & Walczak, 2015;Zhu et al, 2005). However, despite the clear evidence that motor activity is required for mitosis, the temporal and spatial regulation of individual motor proteins throughout mitosis is incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

Distribution of Eg5 and TPX2 in mitosis: Insight from CRISPR tagged cells

Mann

Wadsworth

2018

Cytoskeleton

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The mitotic spindle is a dynamic bipolar structure that mediates chromosome segregation in mitosis. In most organisms, spindle formation requires the action of kinesin-5 motor proteins that generate outward force on antiparallel microtubules to establish spindle bipolarity. Previous work has shown that Eg5 and TPX2, a spindle microtubule-associated protein that suppresses Eg5 motor activity, are enriched on parallel microtubules near spindle poles. This distribution is inconsistent with the requirement for Eg5-dependent force production during mitosis. To investigate this, we used CRISPR/Cas9 gene editing to tag Eg5 and TPX2 with EGFP and quantify protein distribution throughout mitosis. The results show that at metaphase both Eg5-EGFP and TPX2-EGFP are enriched toward spindle poles, but only TPX2-EGFP is enriched relative to microtubules. Eg5-EGFP and TPX2-EGFP show distinct localization patterns in anaphase, with Eg5-EGFP relocalizing to the midzone earlier than TPX2-EGFP. Analysis of spindles oriented at 90° to the coverslip confirmed that Eg5-EGFP was present on bridge microtubules in metaphase and anaphase; in contrast, TPX2 was not enriched, or enriched at later times, on these microtubules. Overall, TPX2 was present at 3.6X the level of Eg5 on the spindle and Eg5 was locally enriched at the prophase centrosome (~7×) compared to the whole cell. Our results show that using cells with fluorescent tags at the endogenous locus can provide novel insight into protein distribution during mitosis.

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“…In summary, the interaction between kinesin-14 members and microtubule minus-ends, microtubule plus-ends and partner proteins can also influence their subcellular localizations and cellular functions, which are crucial in fulfilling their functions and ensure the fidelity of cell division (Yount et al, 2015).…”

Section: Interactions With the Nuclear Import Machinerymentioning

confidence: 99%

Molecular mechanisms of kinesin-14 motors in spindle assembly and chromosome segregation

She

Yang

2017

Journal of Cell Science

102

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During eukaryote cell division, molecular motors are crucial regulators of microtubule organization, spindle assembly, chromosome segregation and intracellular transport. The kinesin-14 motors are evolutionarily conserved minus-end-directed kinesin motors that occur in diverse organisms from simple yeasts to higher eukaryotes. Members of the kinesin-14 motor family can bind to, crosslink or slide microtubules and, thus, regulate microtubule organization and spindle assembly. In this Commentary, we present the common subthemes that have emerged from studies of the molecular kinetics and mechanics of kinesin-14 motors, particularly with regard to their non-processive movement, their ability to crosslink microtubules and interact with the minus-and plusends of microtubules, and with microtubule-organizing center proteins. In particular, counteracting forces between minus-enddirected kinesin-14 and plus-end-directed kinesin-5 motors have recently been implicated in the regulation of microtubule nucleation. We also discuss recent progress in our current understanding of the multiple and fundamental functions that kinesin-14 motors family members have in important aspects of cell division, including the spindle pole, spindle organization and chromosome segregation.

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Regulatory mechanisms that control mitotic kinesins

Cited by 42 publications

References 60 publications

Microtubules, polarity and vertebrate neural tube morphogenesis

Microtubules, polarity and vertebrate neural tube morphogenesis

Distribution of Eg5 and TPX2 in mitosis: Insight from CRISPR tagged cells

Molecular mechanisms of kinesin-14 motors in spindle assembly and chromosome segregation

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