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ATX-2是人类ataxin-2在秀丽隐杆线虫中的同源物,可调节中心体大小和微管动力学。

ATX-2, the C. elegans Ortholog of Human Ataxin-2, Regulates Centrosome Size and Microtubule Dynamics.

作者信息

Stubenvoll Michael D, Medley Jeffrey C, Irwin Miranda, Song Mi Hye

机构信息

Department of Biological Sciences, Oakland University, Rochester, Michigan, United States of America.

出版信息

PLoS Genet. 2016 Sep 30;12(9):e1006370. doi: 10.1371/journal.pgen.1006370. eCollection 2016 Sep.

Abstract

Centrosomes are critical sites for orchestrating microtubule dynamics, and exhibit dynamic changes in size during the cell cycle. As cells progress to mitosis, centrosomes recruit more microtubules (MT) to form mitotic bipolar spindles that ensure proper chromosome segregation. We report a new role for ATX-2, a C. elegans ortholog of Human Ataxin-2, in regulating centrosome size and MT dynamics. ATX-2, an RNA-binding protein, forms a complex with SZY-20 in an RNA-independent fashion. Depleting ATX-2 results in embryonic lethality and cytokinesis failure, and restores centrosome duplication to zyg-1 mutants. In this pathway, SZY-20 promotes ATX-2 abundance, which inversely correlates with centrosome size. Centrosomes depleted of ATX-2 exhibit elevated levels of centrosome factors (ZYG-1, SPD-5, γ-Tubulin), increasing MT nucleating activity but impeding MT growth. We show that ATX-2 influences MT behavior through γ-Tubulin at the centrosome. Our data suggest that RNA-binding proteins play an active role in controlling MT dynamics and provide insight into the control of proper centrosome size and MT dynamics.

摘要

中心体是协调微管动力学的关键位点,并且在细胞周期中其大小会发生动态变化。随着细胞进入有丝分裂,中心体招募更多微管(MT)以形成有丝分裂双极纺锤体,从而确保染色体正确分离。我们报道了线虫中与人类ataxin-2直系同源的ATX-2在调节中心体大小和微管动力学方面的新作用。ATX-2是一种RNA结合蛋白,它以不依赖RNA的方式与SZY-20形成复合物。敲除ATX-2会导致胚胎致死和胞质分裂失败,并能恢复zyg-1突变体的中心体复制。在这条通路中,SZY-20促进ATX-2的丰度,而ATX-2的丰度与中心体大小呈负相关。缺乏ATX-2的中心体显示出中心体因子(ZYG-1、SPD-5、γ-微管蛋白)水平升高,增加了微管成核活性但阻碍了微管生长。我们表明ATX-2通过中心体处的γ-微管蛋白影响微管行为。我们的数据表明RNA结合蛋白在控制微管动力学中发挥积极作用,并为正确控制中心体大小和微管动力学提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4486/5045193/59b14ceca159/pgen.1006370.g001.jpg

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