Kinesin Kip2 enhances microtubule growth in vitro through length-dependent feedback on polymerization and catastrophe

Elife. 2015 Nov 18;4:e10542. doi: 10.7554/eLife.10542.

Abstract

The size and position of mitotic spindles is determined by the lengths of their constituent microtubules. Regulation of microtubule length requires feedback to set the balance between growth and shrinkage. Whereas negative feedback mechanisms for microtubule length control, based on depolymerizing kinesins and severing proteins, have been studied extensively, positive feedback mechanisms are not known. Here, we report that the budding yeast kinesin Kip2 is a microtubule polymerase and catastrophe inhibitor in vitro that uses its processive motor activity as part of a feedback loop to further promote microtubule growth. Positive feedback arises because longer microtubules bind more motors, which walk to the ends where they reinforce growth and inhibit catastrophe. We propose that positive feedback, common in biochemical pathways to switch between signaling states, can also be used in a mechanical signaling pathway to switch between structural states, in this case between short and long polymers.

Keywords: S. cerevisiae; biophysics; cell biology; length regulation; microtubule dynamics; motor protein; positive feedback; structural biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Feedback, Physiological*
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Molecular Motor Proteins / metabolism*
  • Protein Multimerization*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • KIP2 protein, S cerevisiae
  • Microtubule-Associated Proteins
  • Molecular Motor Proteins
  • Saccharomyces cerevisiae Proteins