Depolymerizing kinesins Kip3 and MCAK shape cellular microtubule architecture by differential control of catastrophe

Cell. 2011 Nov 23;147(5):1092-103. doi: 10.1016/j.cell.2011.10.037.

Abstract

Microtubules are dynamic filaments whose ends alternate between periods of slow growth and rapid shortening as they explore intracellular space and move organelles. A key question is how regulatory proteins modulate catastrophe, the conversion from growth to shortening. To study this process, we reconstituted microtubule dynamics in the absence and presence of the kinesin-8 Kip3 and the kinesin-13 MCAK. Surprisingly, we found that, even in the absence of the kinesins, the microtubule catastrophe frequency depends on the age of the microtubule, indicating that catastrophe is a multistep process. Kip3 slowed microtubule growth in a length-dependent manner and increased the rate of aging. In contrast, MCAK eliminated the aging process. Thus, both kinesins are catastrophe factors; Kip3 mediates fine control of microtubule length by narrowing the distribution of maximum lengths prior to catastrophe, whereas MCAK promotes rapid restructuring of the microtubule cytoskeleton by making catastrophe a first-order random process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Physiological Phenomena*
  • Cellular Senescence
  • Humans
  • Kinesin / metabolism*
  • Microtubules / chemistry
  • Microtubules / metabolism*
  • Tubulin / metabolism

Substances

  • Tubulin
  • Kinesin