Changes in microtubule overlap length regulate kinesin-14-driven microtubule sliding

Nat Chem Biol. 2017 Dec;13(12):1245-1252. doi: 10.1038/nchembio.2495. Epub 2017 Oct 16.

Abstract

Microtubule-crosslinking motor proteins, which slide antiparallel microtubules, are required for the remodeling of microtubule networks. Hitherto, all microtubule-crosslinking motors have been shown to slide microtubules at a constant velocity until no overlap remains between them, leading to the breakdown of the initial microtubule geometry. Here, we show in vitro that the sliding velocity of microtubules, driven by human kinesin-14 HSET, decreases when microtubules start to slide apart, resulting in the maintenance of finite-length microtubule overlaps. We quantitatively explain this feedback using the local interaction kinetics of HSET with overlapping microtubules that cause retention of HSET in shortening overlaps. Consequently, the increased HSET density in the overlaps leads to a density-dependent decrease in sliding velocity and the generation of an entropic force that antagonizes the force exerted by the motors. Our results demonstrate that a spatial arrangement of microtubules can regulate the collective action of molecular motors through the local alteration of their individual interaction kinetics.

MeSH terms

  • Humans
  • Kinesins / chemistry
  • Kinesins / metabolism*
  • Kinetics
  • Microtubules / chemistry
  • Microtubules / metabolism*

Substances

  • Kinesins