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WDR62 localizes katanin at spindle poles to ensure synchronous chromosome segregation
Journal of Cell Biology ( IF 7.4 ) Pub Date : 2021-06-17 , DOI: 10.1083/jcb.202007171
Amanda Guerreiro 1 , Filipe De Sousa 1, 2 , Nicolas Liaudet 3 , Daria Ivanova 1 , Anja Eskat 1 , Patrick Meraldi 1, 4
Affiliation  

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.

中文翻译:

WDR62 将剑蛋白定位在纺锤体极,以确保同步染色体分离

WDR62 基因突变会导致原发性小头畸形,这种病理状况通常与细胞分裂缺陷相关,从而导致严重的大脑发育缺陷。然而,WDR62 在有丝分裂纺锤体中的精确功能和定位仍存在争议,因为有人提出它作用于中心体或有丝分裂纺锤体。在这里,我们利用短期 siRNA 蛋白缺失和长期 CRISPR/Cas9 基因敲除技术探索了 WDR62 在人上皮细胞系中的细胞功能。我们证明 WDR62 定位于纺锤体极,促进微管切断酶剑蛋白的募集。由于微管负端解聚不足,WDR62 的耗尽或丢失可稳定纺锤体微管,但不会影响正端微管动力学。在染色体分离过程中,WDR62 和 katanin 促进有效的极地微管通量,并有利于后期极地运动的同步性,以防止滞后染色体。我们推测这些滞后染色体可能与原发性小头畸形的发育缺陷有关。
更新日期:2021-06-17
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