K-fibre minus ends are stabilized by a RanGTP-dependent mechanism essential for functional spindle assembly

Nat Cell Biol. 2011 Nov 13;13(12):1406-14. doi: 10.1038/ncb2372.

Abstract

Chromosome segregation requires the formation of K-fibres, microtubule bundles that attach sister kinetochores to spindle poles. Most K-fibre microtubules originate around the chromosomes through a non-centrosomal RanGTP-dependent pathway and become oriented with the plus ends attached to the kinetochore and the minus ends focused at the spindle poles. The capture and stabilization of microtubule plus ends at the kinetochore has been extensively studied but very little is known on how their minus-end dynamics are controlled. Here we show that MCRS1 is a RanGTP-regulated factor essential for non-centrosomal microtubule assembly. MCRS1 localizes to the minus ends of chromosomal microtubules and K-fibres, where it protects them from depolymerization. Our data reveal the existence of a mechanism that stabilizes the minus ends of chromosomal microtubules and K-fibres, and is essential for the assembly of a functional bipolar spindle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chromosome Segregation / physiology*
  • HeLa Cells
  • Humans
  • Kinesin / genetics
  • Kinesin / metabolism
  • Kinetochores / physiology*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism
  • Mitosis / physiology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Oocytes
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Spindle Apparatus / metabolism*
  • Xenopus
  • beta Karyopherins / metabolism
  • ran GTP-Binding Protein / physiology*

Substances

  • Cell Cycle Proteins
  • KIF2C protein, human
  • MCRS1 protein, human
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • RAN protein, human
  • RNA-Binding Proteins
  • TPX2 protein, human
  • beta Karyopherins
  • Kinesin
  • ran GTP-Binding Protein