WDR62 localizes katanin at spindle poles to ensure synchronous chromosome segregation
| Autor: | Nicolas Liaudet, Patrick Meraldi, Daria Ivanova, Amanda Guerreiro, Filipe Fernandes De Sousa, Anja Eskat |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Time Factors
Cell division Katanin Cell Cycle Proteins Nerve Tissue Proteins Microtubules ddc:616.0757 Spindle pole body Article Chromosome segregation 03 medical and health sciences 0302 clinical medicine Microtubule Chromosome Segregation Humans Disease Spindle Poles ddc:612 Cytoskeleton 030304 developmental biology Anaphase Adenosine Triphosphatases 0303 health sciences Microscopy Confocal biology Cell Biology Spindle apparatus Cell biology Protein Transport Microscopy Fluorescence Centrosome biology.protein Microcephaly 030217 neurology & neurosurgery Cell Cycle and Division HeLa Cells Protein Binding Signal Transduction |
| Zdroj: | The Journal of Cell Biology, Vol. 220, No 8 (2021) P. e202007171 The Journal of Cell Biology |
| ISSN: | 0021-9525 |
| Popis: | Guerreiro et al. show that loss of the primary microcephaly gene WDR62 in human cells mislocalizes the microtubule-severing enzyme katanin from mitotic spindle poles. This mislocalization reduces microtubule minus-end depolymerization, slowing poleward microtubule flux and promoting asynchronous chromosome segregation in anaphase. 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. |
| Databáze: | OpenAIRE |
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