Kif15 functions as an active mechanical ratchet

Molecular Biology of the Cell
Toni McHughRobert A Cross

Abstract

Kif15 is a kinesin-12 that contributes critically to bipolar spindle assembly in humans. Here we use force-ramp experiments in an optical trap to probe the mechanics of single Kif15 molecules under hindering or assisting loads and in a variety of nucleotide states. While unloaded Kif15 is established to be highly processive, we find that under hindering loads, Kif15 takes <∼10 steps. As hindering load is increased, Kif15 forestep:backstep ratio decreases exponentially, with stall occurring at 6 pN. In contrast, under assisting loads, Kif15 detaches readily and rapidly, even from its AMPPNP state. Kif15 mechanics thus depend markedly on the loading direction. Kif15 interacts with a binding partner, Tpx2, and we show that Tpx2 locks Kif15 to microtubules under both hindering and assisting loads. Overall, our data predict that Kif15 in the central spindle will act as a mechanical ratchet, supporting spindle extension but resisting spindle compression.

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Citations

Oct 12, 2019·Life Science Alliance·Willi L Stepp, Zeynep Ökten
Aug 21, 2019·Frontiers in Cell and Developmental Biology·Shijie LiuBrian Storrie
Apr 23, 2020·Analytical Cellular Pathology (Amsterdam)·Yue-Feng SunChao Meng
Feb 12, 2021·Communications Biology·Yohei MaruyamaJunichiro Yajima
Oct 21, 2021·Molecular Biology of the Cell·Marcus A BegleyMary Williard Elting

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