双皮质素家族激酶 ZYG-8DCLK1 可调节微管动力学和马达驱动力,从而促进秀丽隐杆线粒体纺锤体的稳定性。

IF 4 2区 生物学 Q1 GENETICS & HEREDITY PLoS Genetics Pub Date : 2024-09-03 eCollection Date: 2024-09-01 DOI:10.1371/journal.pgen.1011373
Emily R Czajkowski, Yuntong Zou, Nikita S Divekar, Sarah M Wignall
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引用次数: 0

摘要

虽然中心体有助于组织大多数细胞类型的纺锤体,但大多数物种的卵母细胞都缺乏这些结构。在秀丽隐杆线虫卵母细胞的棘突体纺锤体组装过程中,微管负端向外排序,远离染色体,在那里形成两极,但这些向外的力量必须得到平衡,以形成稳定的双极结构。同时,必须精确控制微管动力学,以保持纺锤体的长度和组织。人们对如何调整作用力和动力学以形成稳定的双极结构知之甚少。在这里,我们通过对ZYG-8(一种保守的双皮质素家族激酶)的研究深入了解了这一问题;这种微管相关蛋白的哺乳动物同源物在许多癌症中上调,并与细胞分裂有关,但其发挥作用的机制却鲜为人知。我们发现,卵母细胞中 ZYG-8 的缺失会导致纺锤体过长,并伴有纺锤极和纺锤中段缺陷。重要的是,对单极纺锤的实验显示,ZYG-8 的缺失导致纺锤内的外向力过剩,并提示了该蛋白在调节产生力的马达 BMK-1/kinesin-5 中的潜在作用。此外,我们还发现,ZYG-8 也是卵母细胞纺锤体内微管动力学正常运行的必要条件,而且在减数分裂和有丝分裂过程中,其功能都需要激酶活性。总之,我们的研究结果揭示了 ZYG-8 在卵母细胞中的新作用,并为了解顶体纺锤体如何稳定以促进忠实的减数分裂提供了见解。
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The doublecortin-family kinase ZYG-8DCLK1 regulates microtubule dynamics and motor-driven forces to promote the stability of C. elegans acentrosomal spindles.

Although centrosomes help organize spindles in most cell types, oocytes of most species lack these structures. During acentrosomal spindle assembly in C. elegans oocytes, microtubule minus ends are sorted outwards away from the chromosomes where they form poles, but then these outward forces must be balanced to form a stable bipolar structure. Simultaneously, microtubule dynamics must be precisely controlled to maintain spindle length and organization. How forces and dynamics are tuned to create a stable bipolar structure is poorly understood. Here, we have gained insight into this question through studies of ZYG-8, a conserved doublecortin-family kinase; the mammalian homolog of this microtubule-associated protein is upregulated in many cancers and has been implicated in cell division, but the mechanisms by which it functions are poorly understood. We found that ZYG-8 depletion from oocytes resulted in overelongated spindles with pole and midspindle defects. Importantly, experiments with monopolar spindles revealed that ZYG-8 depletion led to excess outward forces within the spindle and suggested a potential role for this protein in regulating the force-generating motor BMK-1/kinesin-5. Further, we found that ZYG-8 is also required for proper microtubule dynamics within the oocyte spindle and that kinase activity is required for its function during both meiosis and mitosis. Altogether, our findings reveal new roles for ZYG-8 in oocytes and provide insights into how acentrosomal spindles are stabilized to promote faithful meiosis.

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PLoS Genetics
PLoS Genetics GENETICS & HEREDITY-
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期刊介绍: PLOS Genetics is run by an international Editorial Board, headed by the Editors-in-Chief, Greg Barsh (HudsonAlpha Institute of Biotechnology, and Stanford University School of Medicine) and Greg Copenhaver (The University of North Carolina at Chapel Hill). Articles published in PLOS Genetics are archived in PubMed Central and cited in PubMed.
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