Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Nature. 2018 Jul;559(7713):211-216. doi: 10.1038/s41586-018-0279-8. Epub 2018 Jul 4.
Liquid-liquid phase separation has been shown to underlie the formation and disassembly of membraneless organelles in cells, but the cellular mechanisms that control this phenomenon are poorly understood. A prominent example of regulated and reversible segregation of liquid phases may occur during mitosis, when membraneless organelles disappear upon nuclear-envelope breakdown and reappear as mitosis is completed. Here we show that the dual-specificity kinase DYRK3 acts as a central dissolvase of several types of membraneless organelle during mitosis. DYRK3 kinase activity is essential to prevent the unmixing of the mitotic cytoplasm into aberrant liquid-like hybrid organelles and the over-nucleation of spindle bodies. Our work supports a mechanism in which the dilution of phase-separating proteins during nuclear-envelope breakdown and the DYRK3-dependent degree of their solubility combine to allow cells to dissolve and condense several membraneless organelles during mitosis.
液-液相分离被证明是细胞中无膜细胞器形成和解体的基础，但控制这一现象的细胞机制还知之甚少。在有丝分裂过程中，可能会发生一种受调控和可逆的液相间分离的突出例子，此时无膜细胞器在核膜破裂时消失，并在有丝分裂完成时重新出现。在这里，我们表明双特异性激酶 DYRK3 在有丝分裂过程中作为几种类型的无膜细胞器的中心溶解酶发挥作用。DYRK3 激酶活性对于防止有丝分裂细胞质不混合成异常的液体样混合细胞器和纺锤体过度成核是必不可少的。我们的工作支持这样一种机制，即在核膜破裂过程中相分离蛋白的稀释以及 DYRK3 依赖性的蛋白溶解度的程度相结合，使细胞能够在有丝分裂过程中溶解和浓缩几种无膜细胞器。
