Crm1 is a mitotic effector of Ran-GTP in somatic cells

Nat Cell Biol. 2005 Jun;7(6):626-32. doi: 10.1038/ncb1263.


The Ran GTPase controls multiple cellular processes, including nuclear transport, mitotic checkpoints, spindle assembly and post-mitotic nuclear envelope reassembly. Here we examine the mitotic function of Crm1, the Ran-GTP-binding nuclear export receptor for leucine-rich cargo (bearing nuclear export sequence) and Snurportin-1 (ref. 3). We find that Crm1 localizes to kinetochores, and that Crm1 ternary complex assembly is essential for Ran-GTP-dependent recruitment of Ran GTPase-activating protein 1 (Ran-GAP1) and Ran-binding protein 2 (Ran-BP2) to kinetochores. We further show that Crm1 inhibition by leptomycin B disrupts mitotic progression and chromosome segregation. Analysis of spindles within leptomycin B-treated cells shows that their centromeres were under increased tension. In leptomycin B-treated cells, centromeres frequently associated with continuous microtubule bundles that spanned the centromeres, indicating that their kinetochores do not maintain discrete end-on attachments to single kinetochore fibres. Similar spindle defects were observed in temperature-sensitive Ran pathway mutants (tsBN2 cells). Taken together, our findings demonstrate that Crm1 and Ran-GTP are essential for Ran-BP2/Ran-GAP1 recruitment to kinetochores, for definition of kinetochore fibres and for chromosome segregation at anaphase. Thus, Crm1 is a critical Ran-GTP effector for mitotic spindle assembly and function in somatic cells.

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Cell Line, Tumor
  • Chromosome Segregation / physiology
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism
  • HeLa Cells
  • Humans
  • Karyopherins / antagonists & inhibitors
  • Karyopherins / genetics
  • Karyopherins / metabolism*
  • Kinetochores / metabolism*
  • Kinetochores / ultrastructure
  • Microtubules / genetics
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Mitosis / physiology*
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Mutation / physiology
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism
  • Protein Synthesis Inhibitors / pharmacology
  • Protein Transport / physiology
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism*
  • Spindle Apparatus / ultrastructure
  • ran GTP-Binding Protein / genetics
  • ran GTP-Binding Protein / metabolism*


  • GTPase-Activating Proteins
  • Karyopherins
  • Molecular Chaperones
  • Nuclear Pore Complex Proteins
  • Protein Synthesis Inhibitors
  • RANGAP1 protein, human
  • Receptors, Cytoplasmic and Nuclear
  • exportin 1 protein
  • ran-binding protein 2
  • ran GTP-Binding Protein