Kinetochore dynein is required for chromosome motion and congression independent of the spindle checkpoint

Curr Biol. 2007 Jun 5;17(11):973-80. doi: 10.1016/j.cub.2007.04.056. Epub 2007 May 17.

Abstract

During mitosis, the motor molecule cytoplasmic dynein plays key direct and indirect roles in organizing microtubules (MTs) into a functional spindle. At this time, dynein is also recruited to kinetochores, but its role or roles at these organelles remain vague, partly because inhibiting dynein globally disrupts spindle assembly [1-4]. However, dynein can be selectively depleted from kinetochores by disruption of ZW10 [5], and recent studies with this approach conclude that kinetochore-associated dynein (KD) functions to silence the spindle-assembly checkpoint (SAC) [6]. Here we use dynein-antibody microinjection and the RNAi of ZW10 to explore the role of KD in chromosome behavior during mitosis in mammals. We find that depleting or inhibiting KD prevents the rapid poleward motion of attaching kinetochores but not kinetochore fiber (K fiber) formation. However, after kinetochores attach to the spindle, KD is required for stabilizing kinetochore MTs, which it probably does by generating tension on the kinetochore, and in its absence, chromosome congression is defective. Finally, depleting KD reduces the velocity of anaphase chromosome motion by approximately 40%, without affecting the rate of poleward MT flux. Thus, in addition to its role in silencing the SAC, KD is important for forming and stabilizing K fibers and in powering chromosome motion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anaphase / physiology
  • Chromosomal Proteins, Non-Histone / antagonists & inhibitors
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomes / metabolism
  • Chromosomes / physiology
  • Dyneins / physiology*
  • Humans
  • Kinetochores / metabolism*
  • Kinetochores / ultrastructure
  • Microtubule-Associated Proteins / antagonists & inhibitors
  • Microtubule-Associated Proteins / genetics
  • RNA Interference
  • Spindle Apparatus / metabolism*
  • Spindle Apparatus / ultrastructure

Substances

  • Chromosomal Proteins, Non-Histone
  • Microtubule-Associated Proteins
  • ZW10 protein, human
  • Dyneins