Geometry of antiparallel microtubule bundles regulates relative sliding and stalling by PRC1 and Kif4A

Wijeratne, Sithara S.; Subramanian, Radhika

doi:10.7554/elife.32595

Cited by 60 publications

(61 citation statements)

References 71 publications

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“…We have previously shown that MAP65 can organize gliding microtubules into active structures that are reminiscent of cellular architectures in dividing cells 13,14 . MAP65, Ase1, and PRC1 have each been shown to be weakly-associating crosslinkers that can drive microtubule bundling in vitro 15–18 .…”

Section: Introductionmentioning

confidence: 99%

Self-Organization of Spindle-Like Microtubule Structures

Edozie

Sahu

Pitta

et al. 2019

Preprint

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Microtubule self-organization is an important physical process underlying a number of essential cellular functions including cell division. In cell division, the dominant organization is the mitotic spindle, a football-shaped microtubule organization. We are interested in the underlying fundamental principles behind the self-organization of the spindle shape. Prior biological works have hypothesized that motor proteins are required for the proper formation of the spindle. Many of these motor proteins are also microtubule-crosslinkers, so it is unclear if the important aspect is the motor activity or the crosslinking. In this study, we seek to address this question by examining the self-organization of microtubules using crosslinkers alone. We use a minimal system composed of tubulin, an antiparallel microtubule-crosslinking protein, and a crowding agent to explore the phase space of organizations as a function of tubulin and crosslinker concentration. We find that the concentration of the antiparallel crosslinker, MAP65, has a significant effect on the organization and resulted in spindle-like organizations at relatively low concentration without the need for motor activity. Surprisingly, the length of the microtubules only moderately affects the equilibrium organization. We characterize both the shape and dynamics of these spindle-like organizations. We find that they are birefringent homogeneous tactoids. The microtubules have slow mobility, but the crosslinkers have fast mobility within the tactoids. These structures represent a first step in the recapitulation of self-organized spindles of microtubules that can be used as initial structures for further biophysical and active matter studies relevant to the biological process of cell division.

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Section: Introductionmentioning

confidence: 99%

Self-Organization of Spindle-Like Microtubule Structures

Edozie

Sahu

Pitta

et al. 2019

Preprint

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“…In this last section, we consider the situation where sliding results in overlap shrinkage. Specifically, we aim to understand in vitro experiments that showed overlaps remaining for several minutes [1], [9], [26]. This phenomenon occurs when the turnover of crosslinkers is slower than sliding, such that crosslinkers accumulate in the overlap.…”

Section: Steady Overlapsmentioning

confidence: 99%

“…In HeLa cells, PRC1 is required for the stabilisation of the anaphase midzone [29], and has recently been observed to locate to the bridging fibres connecting sister k-fibres, suggesting that this protein may also have a role during metaphase [15]. In vitro, diffusible crosslinkers can oppose sliding by molecular motors [1], [9], [26]. Being passive in nature, one might have expected the force required to move a head to be proportional to the sliding speed.…”

Section: Introductionmentioning

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%

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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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“…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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Geometry of antiparallel microtubule bundles regulates relative sliding and stalling by PRC1 and Kif4A

Cited by 60 publications

References 71 publications

Self-Organization of Spindle-Like Microtubule Structures

Self-Organization of Spindle-Like Microtubule Structures

Theory of antiparallel microtubule overlap stabilization by motors and diffusible crosslinkers

Theory of microtubule length regulation in antiparallel overlaps

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