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Updated: Nov 1, 2025
Reconstitution of Basic Mitotic Spindles in Spherical Emulsion Droplets
Published on: August 13, 2016
WDR62 localizes katanin at spindle poles to ensure synchronous chromosome segregation
Amanda Guerreiro1, Filipe De Sousa1,2, Nicolas Liaudet3
1Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Abstract:
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.
Insights
Mutations in the WDR62 gene cause primary microcephaly. This study shows WDR62 protein localizes to spindle poles, promoting microtubule dynamics crucial for preventing chromosome segregation errors during cell division.
Area of Science:
- Cell Biology
- Genetics
- Developmental Biology
Background:
- Mutations in the WDR62 gene are linked to primary microcephaly, a condition characterized by severe brain developmental defects.
- The exact role and location of WDR62 protein within the mitotic spindle during cell division remain unclear, with proposed functions at centrosomes or on the spindle itself.
Purpose of the Study:
- To investigate the cellular functions and localization of the WDR62 protein in human epithelial cells.
- To elucidate the role of WDR62 in mitotic spindle organization and chromosome segregation.
Main Methods:
- Utilized short-term siRNA to deplete WDR62 protein levels.
- Employed CRISPR/Cas9 gene editing for long-term WDR62 knockout models in human epithelial cell lines.
- Analyzed WDR62 localization at spindle poles and its effect on microtubule dynamics and chromosome segregation.
Main Results:
- Demonstrated that WDR62 localizes to spindle poles and facilitates the recruitment of the microtubule-severing enzyme katanin.
- Showed that WDR62 depletion or absence leads to stabilized spindle microtubules due to impaired minus-end depolymerization, without affecting plus-end dynamics.
- Confirmed that WDR62 and katanin are essential for efficient poleward microtubule flux and synchronized anaphase movements, thereby preventing lagging chromosomes.
Conclusions:
- WDR62 plays a critical role at spindle poles in regulating microtubule dynamics through katanin recruitment.
- The function of WDR62 in ensuring proper chromosome segregation is vital for preventing errors that may contribute to developmental defects observed in primary microcephaly.
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