Cell cycle control of spindle elongation

Roostalu, Johanna; Schiebel, Elmar; Khmelinskii, Anton

doi:10.4161/cc.9.6.11017

Cited by 33 publications

(44 citation statements)

References 102 publications

(143 reference statements)

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“…This bundling of MTs by Ase1p may be facilitated by its structure—it has been proposed that Ase1p is a flexible molecule in solution, which adopts a more rigid conformation only when bundling antiparallel MTs [119]. Second, the resulting Ase1p complex can serve as a key “regulatory hub” for controlling the cell-cycle-dependent localization of various motors and other proteins to the midzone in a system-specific fashion (reviewed in [17]). For example, at anaphase onset in budding yeast, the cell-cycle-regulated de-phosphorylation of Ase1p allows it to recruit kinesin-5 sliding motors to the midzone to drive spindle elongation [120] whereas in Drosophila embryos the Ase1p family member, Feo, partially restricts the association of kinesin-5 sliding motors to the anaphase B spindle midzone (Figure 4) [93].…”

Section: Properties and Functions Of The Molecular Nuts And Bolts mentioning

confidence: 99%

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Anaphase B

Scholey

Civelekoglu-Scholey

Brust‐Mascher

2016

Biology

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Anaphase B spindle elongation is characterized by the sliding apart of overlapping antiparallel interpolar (ip) microtubules (MTs) as the two opposite spindle poles separate, pulling along disjoined sister chromatids, thereby contributing to chromosome segregation and the propagation of all cellular life. The major biochemical “modules” that cooperate to mediate pole–pole separation include: (i) midzone pushing or (ii) braking by MT crosslinkers, such as kinesin-5 motors, which facilitate or restrict the outward sliding of antiparallel interpolar MTs (ipMTs); (iii) cortical pulling by disassembling astral MTs (aMTs) and/or dynein motors that pull aMTs outwards; (iv) ipMT plus end dynamics, notably net polymerization; and (v) ipMT minus end depolymerization manifest as poleward flux. The differential combination of these modules in different cell types produces diversity in the anaphase B mechanism. Combinations of antagonist modules can create a force balance that maintains the dynamic pre-anaphase B spindle at constant length. Tipping such a force balance at anaphase B onset can initiate and control the rate of spindle elongation. The activities of the basic motor filament components of the anaphase B machinery are controlled by a network of non-motor MT-associated proteins (MAPs), for example the key MT cross-linker, Ase1p/PRC1, and various cell-cycle kinases, phosphatases, and proteases. This review focuses on the molecular mechanisms of anaphase B spindle elongation in eukaryotic cells and briefly mentions bacterial DNA segregation systems that operate by spindle elongation.

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Section: Properties and Functions Of The Molecular Nuts And Bolts mentioning

confidence: 99%

“…The focus of the current review is on understanding the basic molecular mechanisms of anaphase B spindle elongation. Reviews of aspects of this topic have been published previously e.g., [15,16,17]. …”

Section: Introduction and Historical Perspectivementioning

confidence: 99%

Anaphase B

Scholey

Civelekoglu-Scholey

Brust‐Mascher

2016

Biology

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“…Notably, despite recent advancements in intravital imaging of certain murine stem cell populations [1][2][3][4], fundamental features of mitotic progression have not been carefully characterized in an adult stem or progenitor cell population. Thus, understanding how the highly dynamic events of mitosis are affected by the broader physiological context within which a cell divides constitutes a significant gap in the field of cell biology.…”

Section: Introductionmentioning

confidence: 98%

Investigating the Regulation of Stem and Progenitor Cell Mitotic Progression by In Situ Imaging

et al. 2015

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Genome stability relies upon efficacious chromosome congression and regulation by the spindle assembly checkpoint (SAC). The study of these fundamental mitotic processes in adult stem and progenitor cells has been limited by the technical challenge of imaging mitosis in these cells in situ. Notably, how broader physiological changes, such as dietary intake or age, affect mitotic progression in stem and/or progenitor cells is largely unknown. Using in situ imaging of C. elegans adult germlines, we describe the mitotic parameters of an adult stem and progenitor cell population in an intact animal. We find that SAC regulation in germline stem and progenitor cells is distinct from that found in early embryonic divisions and is more similar to that of classical tissue culture models. We further show that changes in organismal physiology affect mitotic progression in germline stem and progenitor cells. Reducing dietary intake produces a checkpoint-dependent delay in anaphase onset, and inducing dietary restriction when the checkpoint is impaired increases the incidence of segregation errors in mitotic and meiotic cells. Similarly, developmental aging of the germline stem and progenitor cell population correlates with a decline in the rate of several mitotic processes. These results provide the first in vivo validation of models for SAC regulation developed in tissue culture systems and demonstrate that several fundamental features of mitotic progression in adult stem and progenitor cells are highly sensitive to organismal physiological changes.

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“…28 Eg5 or its homologs are also not required for anaphase in yeast or humans, [28][29][30] during which other molecular components seem to generate the chromosome-segregating force. 31 In the absence of Eg5 activity, spindle bipolarity is maintained by the activity of the plus enddirected kinesin Hklp2/Kif15, which, intriguingly, cannot complement the function of Eg5 in assembling bipolar spindles. 23,32,33 In the Xenopus egg extract system, it has been shown that Eg5…”

Section: Introductionmentioning

confidence: 99%

Modulated microtubule dynamics enable Hklp2/Kif15 to assemble bipolar spindles

Florian

Mayer²

2011

Cell Cycle

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Activity of the sliding motor Eg5 and coordinated microtubule dynamics are both essential for mitotic spindle pole separation. It is still a matter of controversy if changes in microtubule dynamics can compensate inhibition of Eg5 activity and re-enable bipolarization. Using a consistent live cell-imaging approach, we show that perturbation of microtubule dynamics can compensate inhibition of Eg5 through a spindle formation process reminiscent of meiosis: In Eg5-inhibited mammalian somatic cells, alteration of microtubule dynamics through depletion of TOGp or low doses of nocodazole induces the formation of multiple acentrosomal spindle poles which pass through an intermediate multipolar state followed by bipolarization. Pole separation depends on Hklp2/Kif15, an otherwise dispensable plus end-directed spindle motor and results in spindles with two centrosomal poles. Once bipolar, spindles do not rely on altered microtubule dynamics to maintain their bipolarity anymore and are functional in chromosome segregation. We conclude that altered microtubule dynamics enable Hklp2/Kif15 to replace Eg5 in pole separation through a mechanism involving the formation of acentrosomal poles. Our observations suggest that combination chemotherapy regimens involving microtubule-targeting drugs and Eg5 inhibitors might be less effective than expected.

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Cell cycle control of spindle elongation

Cited by 33 publications

References 102 publications

Anaphase B

Anaphase B

Investigating the Regulation of Stem and Progenitor Cell Mitotic Progression by In Situ Imaging

Modulated microtubule dynamics enable Hklp2/Kif15 to assemble bipolar spindles

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