Kinase-controlled phase transition of membraneless organelles in mitosis

Nature. 2018 Jul;559(7713):211-216. doi: 10.1038/s41586-018-0279-8. Epub 2018 Jul 4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome / metabolism
  • Cytoplasm / metabolism
  • Cytoplasmic Granules / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mitosis*
  • Nuclear Envelope / metabolism
  • Organelles / metabolism*
  • Poly(A)-Binding Protein I / metabolism
  • Protein Binding
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / biosynthesis
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Transport
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / biosynthesis
  • Protein-Tyrosine Kinases / metabolism*
  • Solubility
  • Spindle Apparatus / metabolism
  • Stress, Physiological

Substances

  • Poly(A)-Binding Protein I
  • Anaphase-Promoting Complex-Cyclosome
  • DYRK3 protein, human
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases