Making ends meet: how dynein contracts microtubule networks

To better understand important cellular structures we studied networks of stabilized microtubules in Xenopus egg extracts. We found that the molecular motor dynein organizes microtubules into networks of asters and generates large scale contractions by collecting microtubule minus ends.

HFSP Cross-Disciplinary Fellow Sebastian Fürthauer and HFSP Program Grant holder Daniel Needleman and colleagues
authored on Thu, 07 January 2016

Many vital cellular behaviors, such as cell motility, cellular shape changes and cell division, are enabled by the cytoskeleton. Yet, how cytoskeletal motors and filaments self-organize into the networks which drive these behaviors remains poorly understood.  Previously, progress had been slowed by the difficulty of extrapolating from the activity of isolated proteins - which can be gleaned from reconstitution experiments - to their effects in vivo. We circumvent this challenge by studying the behavior of stabilized microtubule networks in Xenopus egg extracts, which capture the full biochemical complexity of a cellular environment.  

Figure: (A): Films of stabilized microtubules spontaneously contract.  (B): We propose that dynein motors (red disks) bind to the minus ends of microtubule (black arrows) and pull them together leading to a contractile stress that is balanced by steric repulsion between colliding microtubules.  (C) The resulting theory (dashed lines) is in quantitative agreement with the observed contraction dynamics (solid lines). Subsequent pairs of lines correspond to different time points. 

In extract, stabilized microtubules self-organized into networks of microtubule asters, which spontaneously contracted to a preferred density. Since dynein is known to be involved in the formation of microtubule asters from previous work, we hypothesized that it also caused the observed contractions.  We thus formulated a theoretical description of network contractions driven by dynein clustering microtubule minus ends.  This theory predicts the dependence of the timescale of contraction on initial network geometry, a development of density inhomogeneities during contraction, a constant final network density, and a strong influence of dynein inhibition on the rate of contraction, all in quantitative agreement with experiments. Interfering with other motors present did not affect the contractile behavior. 

These results demonstrate that motor-driven clustering of filament ends is a generic mechanism to generate contractile tension in a cytoskeletal network, and hints at the role of dynein in shaping important cellular structures.  

Reference 

Active contractions of microtubule networks. Peter J. Foster, Sebastian Fürthauer, Michael J. Shelley, Daniel J. Needleman. eLife 2015;10.7554/eLife.10837 (2015).

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