γ-微管蛋白小复合物的形成对斑马鱼早期胚胎发生至关重要

IF 2.6 Q2 Medicine
Luis Pouchucq , Cristian A. Undurraga , Ricardo Fuentes , Mauricio Cornejo , Miguel L. Allende , Octavio Monasterio
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引用次数: 3

摘要

中心体蛋白γ-微管蛋白是细胞质γ-微管蛋白小复合物(γ-TuSCs)和大复合物(γ-TuRCs)的一部分。分子和细胞证据表明,γ-微管蛋白在微管成核和有丝分裂纺锤体形成中起着核心作用。然而,复合物形成的分子机制及其在动物发育中的生物学作用仍不清楚。在这里,我们在斑马鱼早期胚胎模型中使用γ-微管蛋白基因敲低,以深入了解其在脊椎动物胚胎发生过程中的活性和细胞贡献。γ-微管蛋白功能丧失损害了γ-TuSC的形成,影响了体外微管成核速率。此外,γ-微管蛋白合成的减少导致核动力学和细胞周期进程的显著缺陷,导致发育在原肠中期停滞。在亚细胞水平上,微管的组织和功能发生改变,影响染色体分离,引发细胞增殖阻滞和凋亡。我们的研究结果表明,从头翻译的γ-微管蛋白参与了早期动物发育所需的γ-TuSC的形成。重要的是,这种复合物的形成对于中心体的组装和功能以及细胞增殖都是必不可少的。因此,γ-TuSC的完整性似乎对细胞周期的进展至关重要,同时也对协调早期胚胎进行的许多不同的活动至关重要。我们的发现确定了γ-TuSC在早期脊椎动物胚胎发生调控中的新作用,为未来深入研究γ-微管蛋白的功能及其在发育中的具体作用提供了分子和生化起点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
γ-Tubulin small complex formation is essential for early zebrafish embryogenesis

The centrosomal protein γ-tubulin is part of the cytoplasmic γ-tubulin small (γ-TuSCs) and large complexes (γ-TuRCs). Both, molecular and cellular evidence indicate that γ-tubulin plays a central role in microtubule nucleation and mitotic spindle formation. However, the molecular mechanisms of complex formation and subsequent biological roles in animal development remain unclear. Here, we used γ-tubulin gene knockdown in the zebrafish early embryo model to gain insights into its activity and cellular contribution during vertebrate embryogenesis. γ-Tubulin loss-of-function impaired γ-TuSC formation, impacting the microtubule nucleation rate in vitro. Moreover, decreased γ-tubulin synthesis caused dramatic defects in nuclear dynamics and cell cycle progression, leading to developmental arrest at the mid-gastrula stage. At the subcellular level, microtubule organization and function were altered, affecting chromosome segregation and triggering cell proliferation arrest and apoptosis. Our results suggest that de novo translated γ-tubulin participates in γ-TuSC formation required for early animal development. Importantly, formation of this complex is essential for both centrosome assembly and function, and cell proliferation. Thus, γ-TuSC integrity appears to be critical for cell cycle progression, and concomitantly, for coordinating the many distinct activities carried out by the early embryo. Our findings identify a novel role for γ-TuSC in the regulation of early vertebrate embryogenesis, providing molecular and biochemical starting points for future in depth studies of γ-tubulin functionality and its specific role in development.

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来源期刊
Mechanisms of Development
Mechanisms of Development 生物-发育生物学
CiteScore
3.60
自引率
0.00%
发文量
0
审稿时长
12.4 weeks
期刊介绍: Mechanisms of Development is an international journal covering the areas of cell biology and developmental biology. In addition to publishing work at the interphase of these two disciplines, we also publish work that is purely cell biology as well as classical developmental biology. Mechanisms of Development will consider papers in any area of cell biology or developmental biology, in any model system like animals and plants, using a variety of approaches, such as cellular, biomechanical, molecular, quantitative, computational and theoretical biology. Areas of particular interest include: Cell and tissue morphogenesis Cell adhesion and migration Cell shape and polarity Biomechanics Theoretical modelling of cell and developmental biology Quantitative biology Stem cell biology Cell differentiation Cell proliferation and cell death Evo-Devo Membrane traffic Metabolic regulation Organ and organoid development Regeneration Mechanisms of Development does not publish descriptive studies of gene expression patterns and molecular screens; for submission of such studies see Gene Expression Patterns.
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