The Astrin-SKAP complex reduces friction at the kinetochore-microtubule interface

Curr Biol. 2022 Jun 20;32(12):2621-2631.e3. doi: 10.1016/j.cub.2022.04.061. Epub 2022 May 16.

Abstract

The kinetochore links chromosomes to spindle microtubules to drive chromosome segregation at cell division. While we know nearly all mammalian kinetochore proteins, how these give rise to the strong yet dynamic microtubule attachments required for function remains poorly understood. Here, we focus on the Astrin-SKAP complex, which localizes to bioriented kinetochores and is essential for chromosome segregation but whose mechanical role is unclear. Live imaging reveals that SKAP depletion dampens the movement and decreases the coordination of metaphase sister kinetochores and increases the tension between them. Using laser ablation to isolate kinetochores bound to polymerizing versus depolymerizing microtubules, we show that without SKAP, kinetochores move slower on both polymerizing and depolymerizing microtubules and that more force is needed to rescue microtubules to polymerize. Thus, in contrast to the previously described kinetochore proteins that increase the grip on microtubules under force, Astrin-SKAP reduces the grip, increasing attachment dynamics and force responsiveness and reducing friction. Together, our findings suggest a model where the Astrin-SKAP complex effectively "lubricates" correct, bioriented attachments to help preserve them.

Keywords: Astrin-SKAP; dynamics; force; friction; grip; kinetochore; mammal; mechanics; microtubule; spindle.

Publication types

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

MeSH terms

  • Alcian Blue
  • Animals
  • Cell Cycle Proteins / metabolism
  • Chromosome Segregation
  • Friction
  • Kinetochores* / metabolism
  • Mammals / genetics
  • Microtubule-Associated Proteins* / metabolism
  • Microtubules / metabolism
  • Mitosis
  • Phenazines
  • Phenothiazines
  • Resorcinols
  • Spindle Apparatus / metabolism

Substances

  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Phenazines
  • Phenothiazines
  • Resorcinols
  • astrin
  • Alcian Blue