WDR62 localizes katanin at spindle poles to ensure synchronous chromosome segregation

J Cell Biol. 2021 Aug 2;220(8):e202007171. doi: 10.1083/jcb.202007171. Epub 2021 Jun 17.


Mutations in the WDR62 gene cause primary microcephaly, a pathological condition often associated with defective cell division that results in severe brain developmental defects. The precise function and localization of WDR62 within the mitotic spindle is, however, still under debate, as it has been proposed to act either at centrosomes or on the mitotic spindle. Here we explored the cellular functions of WDR62 in human epithelial cell lines using both short-term siRNA protein depletions and long-term CRISPR/Cas9 gene knockouts. We demonstrate that WDR62 localizes at spindle poles, promoting the recruitment of the microtubule-severing enzyme katanin. Depletion or loss of WDR62 stabilizes spindle microtubules due to insufficient microtubule minus-end depolymerization but does not affect plus-end microtubule dynamics. During chromosome segregation, WDR62 and katanin promote efficient poleward microtubule flux and favor the synchronicity of poleward movements in anaphase to prevent lagging chromosomes. We speculate that these lagging chromosomes might be linked to developmental defects in primary microcephaly.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromosome Segregation*
  • HeLa Cells
  • Humans
  • Microcephaly / genetics
  • Microcephaly / metabolism
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Microtubules / enzymology*
  • Microtubules / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Binding
  • Protein Transport
  • Signal Transduction
  • Spindle Poles / enzymology*
  • Spindle Poles / genetics
  • Time Factors


  • Cell Cycle Proteins
  • Nerve Tissue Proteins
  • WDR62 protein, human
  • Adenosine Triphosphatases
  • KATNB1 protein, human