Spindle morphology changes between meiosis and mitosis driven by CK2 regulation of the Ran pathway.

IF 7.4 1区 生物学 Q1 CELL BIOLOGY
Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-07-01 DOI:10.1083/jcb.202407154
Helena Cantwell, Hieu Nguyen, Arminja N Kettenbach, Rebecca Heald
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Abstract

The transition from meiotic divisions in the oocyte to embryonic mitoses is a critical step in animal development. Despite negligible changes to cell size and shape, following fertilization the small, barrel-shaped meiotic spindle is replaced by a large zygotic spindle that nucleates abundant astral microtubules at spindle poles. To probe underlying mechanisms, we applied a drug treatment approach using Ciona eggs and found that inhibition of casein kinase 2 (CK2) caused a shift from meiotic to mitotic-like spindle morphology with nucleation of robust astral microtubules, an effect reproduced in Xenopus egg cytoplasmic extracts. In both species, CK2 activity decreased at fertilization. Phosphoproteomic differences between Xenopus meiotic and mitotic extracts that also accompanied CK2 inhibition pointed to RanGTP-regulated factors as potential targets. Interfering with RanGTP-driven microtubule formation suppressed astral microtubule growth caused by CK2 inhibition. These data support a model in which CK2 activity attenuation at fertilization leads to activation of RanGTP-regulated microtubule effectors, inducing mitotic spindle morphology.

CK2调控Ran通路驱动减数分裂和有丝分裂纺锤体形态的变化。
从卵母细胞的减数分裂到胚胎有丝分裂的转变是动物发育的关键步骤。尽管细胞的大小和形状发生了微小的变化,但受精后,小的桶形减数分裂纺锤体被一个大的合子纺锤体所取代,在纺锤极形成丰富的星状微管。为了探究其潜在的机制,我们采用了一种使用爪蟾卵的药物治疗方法,发现酪蛋白激酶2 (CK2)的抑制导致爪蟾卵从减数分裂转变为有丝分裂样纺锤体形态,并形成强大的星状微管,这种效应在爪蟾卵细胞质提取物中重现。在这两个物种中,CK2活性在受精时都有所下降。非洲爪蟾减数分裂和有丝分裂提取物之间的磷酸化蛋白质组学差异也伴随着CK2的抑制,这表明rangtp调节因子是潜在的靶点。干扰rangtp驱动的微管形成可抑制CK2抑制引起的星状微管生长。这些数据支持一个模型,即受精时CK2活性衰减导致rangtp调控的微管效应物激活,诱导有丝分裂纺锤体形态。
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来源期刊
Journal of Cell Biology
Journal of Cell Biology 生物-细胞生物学
CiteScore
12.60
自引率
2.60%
发文量
213
审稿时长
1 months
期刊介绍: The Journal of Cell Biology (JCB) is a comprehensive journal dedicated to publishing original discoveries across all realms of cell biology. We invite papers presenting novel cellular or molecular advancements in various domains of basic cell biology, along with applied cell biology research in diverse systems such as immunology, neurobiology, metabolism, virology, developmental biology, and plant biology. We enthusiastically welcome submissions showcasing significant findings of interest to cell biologists, irrespective of the experimental approach.
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