Two modes of PRC1-mediated mechanical resistance to kinesin-driven microtubule network disruption

Curr Biol. 2021 Jun 21;31(12):2495-2506.e4. doi: 10.1016/j.cub.2021.03.034. Epub 2021 Apr 12.


The proper organization of the microtubule-based spindle during cell division requires the collective activity of many different proteins. These include non-motor microtubule-associated proteins (MAPs), whose functions include crosslinking microtubules to regulate filament sliding rates and assemble microtubule arrays. One such protein is PRC1, an essential MAP that has been shown to preferentially crosslink overlapping antiparallel microtubules at the spindle midzone. PRC1 has been proposed to act as a molecular brake, but insight into the mechanism of how PRC1 molecules function cooperatively to resist motor-driven microtubule sliding and to allow for the formation of stable midzone overlaps remains unclear. Here, we employ a modified microtubule gliding assay to rupture PRC1-mediated microtubule pairs using surface-bound kinesins. We discovered that PRC1 crosslinks always reduce bundled filament sliding velocities relative to single-microtubule gliding rates and do so via two distinct emergent modes of mechanical resistance to motor-driven sliding. We term these behaviors braking and coasting, where braking events exhibit substantially slowed microtubule sliding compared to coasting events. Strikingly, braking behavior requires the formation of two distinct high-density clusters of PRC1 molecules near microtubule tips. Our results suggest a cooperative mechanism for PRC1 accumulation when under mechanical load that leads to a unique state of enhanced resistance to filament sliding and provides insight into collective protein ensemble behavior in regulating the mechanics of spindle assembly.

Keywords: PRC1; biophysics; central spindle; cytoskeleton; kinesin; microtubule-associated proteins; microtubules; mitosis; spindle mechanics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • Humans
  • Kinesins / metabolism*
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism*
  • Spindle Apparatus / chemistry
  • Spindle Apparatus / metabolism


  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • PRC1 protein, human
  • Kinesins