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极光激酶A在小鼠卵母细胞减数分裂纺锤体构建中的时空需求

Spatio-temporal requirements of Aurora kinase A in mouse oocyte meiotic spindle building.

作者信息

Blengini Cecilia S, Vaskovicova Michaela, Schier Jan, Drutovic David, Schindler Karen

机构信息

Department of Genetics, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA.

Human Genetics Institute of New Jersey, Piscataway, NJ 08854, USA.

出版信息

iScience. 2024 Jul 3;27(8):110451. doi: 10.1016/j.isci.2024.110451. eCollection 2024 Aug 16.

Abstract

Meiotic spindles are critical to ensure chromosome segregation during gamete formation. Oocytes lack centrosomes and use alternative microtubule-nucleation mechanisms for spindle building. How these mechanisms are regulated is still unknown. Aurora kinase A (AURKA) is essential for mouse oocyte meiosis because in pro-metaphase I it triggers microtubule organizing-center fragmentation and its expression compensates for the loss of the two other Aurora kinases (AURKB/AURKC). Although knockout mouse models were useful for foundational studies, AURK spatial and temporal functions are not yet resolved. We provide high-resolution analyses of AURKA/AURKC requirements during meiotic spindle-building and identify the subcellular populations that carry out these functions: 1) AURKA is required in early spindle assembly and later for spindle stability, whereas 2) AURKC is required in late pro-metaphase, and 3) Targeted AURKA constructs expressed in triple AURK knockout oocytes reveal that spindle pole-localized AURKA is the most important population controlling spindle building and stability mechanisms.

摘要

减数分裂纺锤体对于确保配子形成过程中的染色体分离至关重要。卵母细胞缺乏中心体,并利用替代的微管成核机制来构建纺锤体。这些机制是如何被调控的仍然未知。极光激酶A(AURKA)对小鼠卵母细胞减数分裂至关重要,因为在减数分裂前期I,它会触发微管组织中心碎片化,并且其表达可补偿另外两种极光激酶(AURKB/AURKC)的缺失。尽管基因敲除小鼠模型对基础研究很有用,但AURK的时空功能尚未明确。我们对减数分裂纺锤体构建过程中AURKA/AURKC的需求进行了高分辨率分析,并确定了执行这些功能的亚细胞群体:1)AURKA在纺锤体早期组装时是必需的,后期对纺锤体稳定性也是必需的;而2)AURKC在减数分裂前期末是必需的;3)在三联极光激酶基因敲除的卵母细胞中表达的靶向AURKA构建体表明,定位于纺锤体极的AURKA是控制纺锤体构建和稳定机制的最重要群体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21ef/11284559/35b8a6b36f4c/fx1.jpg

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