Determinants of Polar versus Nematic Organization in Networks of Dynamic Microtubules and Mitotic Motors

Johanna Roostalu,Jamie Rickman,Claire Thomas,François Nédélec,Thomas Surrey

doi:10.1016/j.cell.2018.09.029

Johanna Roostalu, Jamie Rickman + Show 3 more

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https://doi.org/10.1016/j.cell.2018.09.029

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Abstract

SummaryDuring cell division, mitotic motors organize microtubules in the bipolar spindle into either polar arrays at the spindle poles or a “nematic” network of aligned microtubules at the spindle center. The reasons for the distinct self-organizing capacities of dynamic microtubules and different motors are not understood. Using in vitro reconstitution experiments and computer simulations, we show that the human mitotic motors kinesin-5 KIF11 and kinesin-14 HSET, despite opposite directionalities, can both organize dynamic microtubules into either polar or nematic networks. We show that in addition to the motor properties the natural asymmetry between microtubule plus- and minus-end growth critically contributes to the organizational potential of the motors. We identify two control parameters that capture system composition and kinetic properties and predict the outcome of microtubule network organization. These results elucidate a fundamental design principle of spindle bipolarity and establish general rules for active filament network organization.

Highlights

The internal organization of eukaryotic cells depends on cytoskeletal networks
Using in vitro reconstitution experiments and computer simulations, we show that the human mitotic motors kinesin-5 KIF11 and kinesin-14 HSET, despite opposite directionalities, can both organize dynamic microtubules into either polar or nematic networks
KIF11 Organizes Dynamic Microtubules into Nematic Networks To establish asymmetric microtubule growth dynamics in vitro and mimic the situation in the cell, we used a C-terminal fragment of the human microtubule minus-end stabilizer CAMSAP3 (CAMSAP3-C) (Figures 1A and S1) (Atherton et al, 2017; Hendershott and Vale, 2014; Jiang et al, 2014)

Summary

Introduction

The internal organization of eukaryotic cells depends on cytoskeletal networks. Dynamic microtubules and actin filaments, motile crosslinkers, and other associated proteins drive active networks into a variety of organizational states required for distinct cell functions (Helmke et al, 2013; Sanchez and Feldman, 2017). In large cells of embryos and plants motors mediate the formation of arrays of aligned microtubules or actin filaments, causing global cytoplasmic flows to distribute nutrients and organelles (Ganguly et al, 2012; Goldstein et al, 2008; Monteith et al, 2016; Palacios and St Johnston, 2002). These networks consisting of aligned filaments of mixed-polarity are called ‘‘nematic,’’ a term borrowed from liquid crystal terminology (Needleman and Dogic, 2017). How cells control the organization of active filament networks with different topologies is an open question

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