A Force-Induced Directional Switch of a Molecular Motor Enables Parallel Microtubule Bundle Formation

Cell. 2016 Oct 6;167(2):539-552.e14. doi: 10.1016/j.cell.2016.09.029.

Abstract

Microtubule-organizing centers (MTOCs) nucleate microtubules that can grow autonomously in any direction. To generate bundles of parallel microtubules originating from a single MTOC, the growth of multiple microtubules needs to coordinated, but the underlying mechanism is unknown. Here, we show that a conserved two-component system consisting of the plus-end tracker EB1 and the minus-end-directed molecular motor Kinesin-14 is sufficient to promote parallel microtubule growth. The underlying mechanism relies on the ability of Kinesin-14 to guide growing plus ends along existing microtubules. The generality of this finding is supported by yeast, Drosophila, and human EB1/Kinesin-14 pairs. We demonstrate that plus-end guiding involves a directional switch of the motor due to a force applied via a growing microtubule end. The described mechanism can account for the generation of parallel microtubule networks required for a broad range of cellular functions such as spindle assembly or cell polarization.

Keywords: Cik1-Kar3; EB1; Parallel microtubules; directional switch; kinesin-14; microtubule polymerization; plus-end guiding; polarization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism*
  • DNA Helicases / metabolism*
  • Drosophila melanogaster
  • Humans
  • Kinesins / metabolism*
  • Mechanical Phenomena
  • Microtubule Proteins / metabolism*
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Molecular Motor Proteins / metabolism*
  • Oncogene Proteins / metabolism*
  • RNA Helicases / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • BIM1 protein, S cerevisiae
  • Cell Cycle Proteins
  • KAR3 protein, S cerevisiae
  • Microtubule Proteins
  • Microtubule-Associated Proteins
  • Molecular Motor Proteins
  • Oncogene Proteins
  • Saccharomyces cerevisiae Proteins
  • KIF14 protein, human
  • SEN1 protein, S cerevisiae
  • DNA Helicases
  • RNA Helicases
  • Kinesins