Pivot-and-bond model explains microtubule bundle formation

Prelogović, Marcel; Winters, Lora; Milas, Ana; Tolić, Iva Marija; Pavin, Nenad

doi:10.1101/157719

Cited by 5 publications

(6 citation statements)

References 46 publications

(47 reference statements)

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“…We have recently introduced a pivot-and-bond model, in which microtubules pivot around the spindle pole and bond with each other by crosslinking proteins (Prelogović et al 2017 ). Our experiments in fission yeast show that microtubules pivot around the spindle pole before getting aligned and forming a parallel bundle, and that bundle formation relies to a large extent on the crosslinker anaphase spindle elongation protein (Ase1), a homolog of the human protein regulator of cytokinesis 1 (PRC1) (Prelogović et al 2017 ). Thus, in the pivot-and-bond model, microtubules explore the space by performing rotational diffusion and ultimately approach one another, which in turn allows the crosslinking proteins to connect the microtubules into a stable parallel bundle.…”

Section: Kinetochore Fibersmentioning

confidence: 99%

Mitotic spindle: kinetochore fibers hold on tight to interpolar bundles

Tolić

2017

Eur Biophys J

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When a cell starts to divide, it forms a spindle, a micro-machine made of microtubules, which separates the duplicated chromosomes. The attachment of microtubules to chromosomes is mediated by kinetochores, protein complexes on the chromosome. Spindle microtubules can be divided into three major classes: kinetochore microtubules, which form k-fibers ending at the kinetochore; interpolar microtubules, which extend from the opposite sides of the spindle and interact in the middle; and astral microtubules, which extend towards the cell cortex. Recent work in human cells has shown a close relationship between interpolar and kinetochore microtubules, where interpolar bundles are attached laterally to kinetochore fibers almost all along their length, acting as a bridge between sister k-fibers. Most of the interpolar bundles are attached to a pair of sister kinetochore fibers and vice versa. Thus, the spindle is made of modules consisting of a pair of sister kinetochore fibers and a bundle of interpolar microtubules that connects them. These interpolar bundles, termed bridging fibers, balance the forces acting at kinetochores and support the rounded shape of the spindle during metaphase. This review discusses the structure, function, and formation of kinetochore fibers and interpolar bundles, with an emphasis on how they interact. Their connections have an impact on the force balance in the spindle and on chromosome movement during mitosis because the forces in interpolar bundles are transmitted to kinetochore fibers and hence to kinetochores through these connections.

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Section: Kinetochore Fibersmentioning

confidence: 99%

Mitotic spindle: kinetochore fibers hold on tight to interpolar bundles

Tolić

2017

Eur Biophys J

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“…In general, pivoting helps the MTs as they search for targets such as kinetochores 29,56,60 , cortical anchors in vivo 58 and in vitro 61 , or other MTs (ref. 30,59 ). This motion allows MTs to swipe through space, which increases the explored volume and makes the search process more efficient 2,62 .…”

Section: Discussionmentioning

confidence: 99%

“…29 , which is consistent with ref. 30 . For MT lengths, we assume they follow an exponential distribution.…”

Section: Methodsmentioning

confidence: 99%

“…Indeed, live-cell imaging in fission yeast showed that MTs change their angle as they rotate (i.e., pivot) around the spindle pole 29 . Eventually these MTs join the spindle, with help from Ase1 crosslinkers 30 . Experiments on budding yeast showed that cells lacking kinesin-14 motors have more MTs extending at an oblique angle with respect to the spindle and fewer antiparallel MTs than wild-type cells do 31 .…”

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Pivoting of microtubules driven by minus end directed motors leads to their alignment to form an interpolar bundle

Winters

Ban

Prelogović

et al. 2018

Preprint

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At the beginning of mitosis, the cell forms a spindle made of microtubules and associated proteins to segregate chromosomes. An important part of spindle architecture is a set of antiparallel microtubule bundles connecting the two spindle poles. A key question is how microtubules extending at arbitrary angles form an antiparallel interpolar bundle. Here we show that microtubules meet at an oblique angle and subsequently rotate into antiparallel alignment. By combining experiments with theory, we show that microtubules from each pole search for those from the opposite pole by performing random angular movement. Upon contact of two microtubules, they slide sideways along each other towards the minus end, which we interpret as the action of minus end directed Cut7/kinesin-5 motors. In conclusion, random rotational motion helps microtubules from the opposite poles to find each other and subsequent accumulation of motors allows them to generate forces that drive interpolar bundle formation.

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“…In these simulations, antiparallel crosslinking by Ase1 and the stabilization of crosslinked MT dynamics are sufficient for model bipolar spindle assembly in the absence of motors [51]. Related previous theory has studied mitotic MT bundling by motors and crosslinkers [73,74].…”

Section: Introductionmentioning

confidence: 86%

Theory of cytoskeletal reorganization during crosslinker-mediated mitotic spindle assembly

Lamson¹,

Edelmaier²,

Glaser³

et al. 2018

Preprint

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Cells grow, move, and respond to outside stimuli by large-scale cytoskeletal reorganization. A prototypical example of cytoskeletal remodeling is mitotic spindle assembly, during which microtubules nucleate, undergo dynamic instability, bundle, and organize into a bipolar spindle. Key mechanisms of this process include regulated filament polymerization, crosslinking, and motor-protein activity. Remarkably, using passive crosslinkers, fission yeast can assemble a bipolar spindle in the absence of motor proteins. We develop a torque-balance model that describes this reorganization due to dynamic microtubule bundles, spindle-pole bodies, the nuclear envelope, and passive crosslinkers to predict spindle-assembly dynamics. We compare these results to those obtained with kinetic Monte Carlo-Brownian dynamics simulations, which include crosslinker-binding kinetics and other stochastic effects. Our results show that rapid crosslinker reorganization to microtubule overlaps facilitates crosslinker-driven spindle assembly, a testable prediction for future experiments. Combining these two modeling techniques, we illustrate a general method for studying cytoskeletal network reorganization.

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Pivot-and-bond model explains microtubule bundle formation

Cited by 5 publications

References 46 publications

Mitotic spindle: kinetochore fibers hold on tight to interpolar bundles

Mitotic spindle: kinetochore fibers hold on tight to interpolar bundles

Pivoting of microtubules driven by minus end directed motors leads to their alignment to form an interpolar bundle

Theory of cytoskeletal reorganization during crosslinker-mediated mitotic spindle assembly

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