Self-Organization of Minimal Anaphase Spindle Midzone Bundles

Hannabuss, Jonathon; Lera-Ramírez, Manuel; Cade, Nicholas I.; Fourniol, Franck J.; Nédélec, François; Surrey, Thomas

doi:10.1016/j.cub.2019.05.049

Cited by 48 publications

(73 citation statements)

References 43 publications

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“…Interestingly, fission yeast cells reduce the turnover of Ase1 upon anaphase entry, where maintenance of overlaps at the central spindle is important for the separation of spindle poles, suggesting that turnover regulation is active in cells [3]. Upon the action of only a few motors, the crosslinkers form stable overlaps, as observed experimentally [4]. The length of such overlap is determined by a simple rule: the overlap decreases until crosslinkers reach their maximal density.…”

Section: Discussionmentioning

confidence: 75%

“…F.J.N is supported by the Gatsby foundation. We thank S. Diez, M. Braun and T. Surrey for discussion and all the authors of [4] which inspired this work. We thank S. Dmitrieff for critical reading of the manuscript.…”

Section: Acknowledgmentsmentioning

confidence: 99%

“…Statistically, overlap extension creates more possibilities for the crosslinkers to bind, resulting in an entropic pressure effectively pushing the microtubules ends apart. Inversely, when sliding results in the densification of the crosslinkers in the overlap, the resistance to sliding increases, eventually reaching a steady state overlap length, which can remain stable for several minutes [1], [9], [27], [4].…”

Section: Introductionmentioning

confidence: 99%

“…This was explored with Kinesin-14 and Ase1 [1], [9]. Another system in which Kif4A motors directly pulled on PRC1 crosslinkers was modelled previously by us [4], and thus omitted here. These systems offer gradual complexity and different outcome.…”

Section: Introductionmentioning

confidence: 99%

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Theory of antiparallel microtubule overlap stabilization by motors and diffusible crosslinkers

Lera-Ramírez

Nédélec

2019

Preprint

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Antiparallel microtubule bundles are essential structural elements of many cytoskeletal structures, for instance the mitotic spindle. In such bundles, neighbouring microtubules are bonded by specialised crosslinkers of the Ase1/PRC1/MAP65 family that can diffuse longitudinally along microtubules. Similarly, some kinesin motors implicated in bundle formation have a diffusible tail allowing them to slide passively along microtubules. We develop here a theory of two microtubules connected by motors and diffusible connectors, in different configurations that can be realized experimentally. In all cases, the microtubule sliding speed derived analytically is validated by stochastic simulations and used to discuss recent experimental results, such as force generation by kinesin-14, and overlap stabilization by Ase1. Some systems can produce steady overlaps that are determined by the density of crosslinkers on the microtubule lattice. This property naturally leads to robust coordination between sliding and growth in dynamic bundles of microtubules, an essential property in mitosis.

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Section: Discussionmentioning

confidence: 75%

Section: Acknowledgmentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Theory of antiparallel microtubule overlap stabilization by motors and diffusible crosslinkers

Lera-Ramírez

Nédélec

2019

Preprint

Self Cite

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“…Previous work has examined how antiparallel sliding motors such as kinesin-5 motors, which tend to separate overlapping filaments, and crosslinking proteins from the PRC1/Ase1/MAP65 family, which tend to increase overlap length [16], can balance to give stable overlaps [17][18][19]. Length-regulated overlaps can be created in vitro via crosslinkers and motors that bind to the crosslinkers and exert force on them [20][21][22]. In addition, Bieling and Surrey experimentally demonstrated regulated antiparallel MT overlaps in a system in which little to no sliding occurs [23].…”

mentioning

confidence: 99%

Theory of microtubule length regulation in antiparallel overlaps

Kuan

Betterton

2019

Preprint

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During cell division, microtubules in the mitotic spindle form antiparallel overlaps near the center of the spindle. Kinesin motor proteins alter microtubule polymerization dynamics to regulate the length of these overlaps to maintain spindle integrity. Length regulation of antiparallel overlaps has been reconstituted with purified microtubules, crosslinkers, and motors. Here we develop a theory of steady-state overlap length which depends on the filament plus-end motor concentration, determined by a balance between motor arrival (motor binding and stepping in the overlap) and motor departure (motor unbinding from filament tips during depolymerization) in the absence of motor-driven sliding. Assuming that motors processively depolymerize and exhibit altered binding kinetics near MT plus-ends improves the agreement between theory and experiment. Our theory explains the origin of the experimentally observed critical concentration, a minimum motor concentration to observe a steady-state overlap length.

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Theory of antiparallel microtubule overlap stabilization by motors and diffusible crosslinkers

Lera-Ramírez

Nédélec

2019

Cytoskeleton

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Antiparallel microtubule bundles are essential structural elements of many cytoskeletal structures, for instance, the mitotic spindle. Sliding of microtubules relative to each other can lead to an overall elongation of the bundle. However, such sliding must be accompanied by microtubule growth, to maintain the overlap, which is a landmark of anaphase. Diffusive crosslinkers of the Ase1/PRC1/MAP65 family are able to form stable overlaps in combination with kinesin‐14 motors. This process is thought to arise through a balance of forces between motors and crosslinkers, the latter effectively producing an entropic pressure. We provide a continuous theory to explain the formation of stable overlaps, in which steric effects caused by the finite number of binding sites available on the microtubule lattice play a leading role. We confirmed the validity of this approach using discrete stochastic simulations performed with the Open Source simulation engine Cytosim. From the densities of motors and crosslinkers, their diffusion rates, and the velocities of motors, the theory predicts the sliding speed of microtubules and explains the force production and breaking effect of crosslinkers and motors containing diffusible microtubule‐binding domains. Finally, we discuss a mechanism by which sliding and microtubule growth can be coordinated without the need for fine‐tuning the parameters of the system, in line with the known robustness of mitosis.

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Self-Organization of Minimal Anaphase Spindle Midzone Bundles

Cited by 48 publications

References 43 publications

Theory of antiparallel microtubule overlap stabilization by motors and diffusible crosslinkers

Theory of antiparallel microtubule overlap stabilization by motors and diffusible crosslinkers

Theory of microtubule length regulation in antiparallel overlaps

Theory of antiparallel microtubule overlap stabilization by motors and diffusible crosslinkers

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