2016年7月4日讯 /生物谷BIOON/ --来自奥地利科学院分子生物技术研究所的研究人员最近发现一种蛋白质能够在细胞分裂过程中帮助染色体彼此分离开来。相关研究结果发表在国际学术期刊Nature上。 每天你的体内都有几十亿个细胞在进行分裂。细胞分裂能够促进身体生长,还会替代皮肤,血液以及肠道等器官中衰老的细胞。细胞分裂要经历细胞周期中的不同阶段,在细胞周期的大部分时间内细胞都在进行基因表达。随着细胞周期的进行,复制形成的染色体会在纺锤体的作用下逐渐分开。 在细胞进行分裂之前,染色体会进行复制,并发生形态学变化,新形成的两条染色单体变成类似X形状,随着细胞分裂进入后期,两条染色单体会在纺锤体的作用下各自向细胞两端移动,最终构成两个子代细胞的基因组。但是细胞分裂过程中染色体如何保证各自的“独立性”仍然是一个迷。 由Daniel Gerlich领导的研究团队发现分裂期细胞内的Ki-67蛋白能够防止染色体彼此粘连在一起。众所周知Ki-67是一个表示增殖细胞的标记物分子,常用于癌症诊断过程中细胞异常分裂的检测,但是人们对Ki-67的功能了解较少。研究人员发现缺失Ki-67的情况下,染色体仍然会正常形成但是所有染色体会变成一团粘在一起无法移动,缺少Ki-67的细胞其分裂过程也会变慢。 研究人员进一步确定了Ki-67 如何促进染色体的分离。文章第一作者Sara Cuylen这样解释道:“Ki-67的一端会结合在染色体上,而另一端会伸向远离染色体的地方,这样Ki-67就会在染色体表面形成拉长的刷子样结构,最为重要的是可以形成屏障将不同染色体彼此分开。”研究人员表示,Ki-67的这些特性让人联想到破坏尘垢和油渍的表面活性剂,他们完全没想到Ki-67在细胞内发挥了类似表面活性剂的功能。 Daniel Gerlich指出表面活性剂机制可能还适用于其他细胞器的空间排列,找到其他具有表面活性剂特性的蛋白分子研究其在细胞内部成分的空间排列方面的作用将有重要意义。(生物谷Bioon.com) 本文系生物谷原创编译整理,欢迎转载! Ki-67 acts as a biological surfactant to disperse mitotic chromosomes Sara Cuylen, Claudia Blaukopf, Antonio Z. Politi, Thomas Müller-Reichert, Beate Neumann, Ina Poser, Jan Ellenberg, Anthony A. Hyman & Daniel W. Gerlich Eukaryotic genomes are partitioned into chromosomes that form compact and spatially well-separated mechanical bodies during mitosis1, 2, 3. This enables chromosomes to move independently of each other for segregation of precisely one copy of the genome to each of the nascent daughter cells. Despite insights into the spatial organization of mitotic chromosomes4 and the discovery of proteins at the chromosome surface3, 5, 6, the molecular and biophysical bases of mitotic chromosome structural individuality have remained unclear. Here we report that the proliferation marker protein Ki-67 (encoded by the MKI67 gene), a component of the mitotic chromosome periphery, prevents chromosomes from collapsing into a single chromatin mass after nuclear envelope disassembly, thus enabling independent chromosome motility and efficient interactions with the mitotic spindle. The chromosome separation function of human Ki-67 is not confined within a specific protein domain, but correlates with size and net charge of truncation mutants that apparently lack secondary structure. This suggests that Ki-67 forms a steric and electrostatic charge barrier, similar to surface-active agents (surfactants) that disperse particles or phase-separated liquid droplets in solvents. Fluorescence correlation spectroscopy showed a high surface density of Ki-67 and dual-colour labelling of both protein termini revealed an extended molecular conformation, indicating brush-like arrangements that are characteristic of polymeric surfactants. Our study thus elucidates a biomechanical role of the mitotic chromosome periphery in mammalian cells and suggests that natural proteins can function as surfactants in intracellular compartmentalization. |
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