Max Planck Institute for the Physics of Complex Systems, Nö\x{0308}thnitzer Strasse 38, 01187 Dresden, Germany; and.
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Proc Natl Acad Sci U S A. 2014 Jul 1;111(26):E2636-45. doi: 10.1073/pnas.1404855111. Epub 2014 Jun 16.
Centrosomes are highly dynamic, spherical organelles without a membrane. Their physical nature and their assembly are not understood. Using the concept of phase separation, we propose a theoretical description of centrosomes as liquid droplets. In our model, centrosome material occurs in a form soluble in the cytosol and a form that tends to undergo phase separation from the cytosol. We show that an autocatalytic chemical transition between these forms accounts for the temporal evolution observed in experiments. Interestingly, the nucleation of centrosomes can be controlled by an enzymatic activity of the centrioles, which are present at the core of all centrosomes. This nonequilibrium feature also allows for multiple stable centrosomes, a situation that is unstable in equilibrium phase separation. Our theory explains the growth dynamics of centrosomes for all cell sizes down to the eight-cell stage of the Caenorhabditis elegans embryo, and it also accounts for data acquired in experiments with aberrant numbers of centrosomes and altered cell volumes. Furthermore, the model can describe unequal centrosome sizes observed in cells with perturbed centrioles. We also propose an interpretation of the molecular details of the involved proteins in the case of C. elegans. Our example suggests a general picture of the organization of membraneless organelles.
中心体是高度动态的、无膜的球形细胞器。其物理性质及其组装尚不清楚。我们使用相分离的概念,提出了将中心体描述为液滴的理论模型。在我们的模型中,中心体物质以可溶于细胞质的形式和一种倾向于与细胞质发生相分离的形式存在。我们表明,这些形式之间的自动催化化学转变解释了实验中观察到的时间演化。有趣的是,中心体的成核可以通过中心粒的酶活性来控制,中心粒存在于所有中心体的核心。这种非平衡特征还允许存在多个稳定的中心体,这种情况在平衡相分离中是不稳定的。我们的理论解释了所有细胞大小的中心体的生长动力学,直到秀丽隐杆线虫胚胎的八细胞阶段,并且还解释了实验中获得的具有异常数量的中心体和改变的细胞体积的数据。此外,该模型可以描述在受干扰的中心粒的细胞中观察到的不等的中心体大小。我们还提出了在秀丽隐杆线虫的情况下涉及蛋白质的分子细节的解释。我们的例子提出了一个无膜细胞器的组织的一般图像。